Biphenyl derivatives substituted with an aromatic or heteroaromatic radical, and pharmaceutical and cosmetic compositions containing them

ABSTRACT

Compounds of formula (I): 
                         
in which:
         Ar represents an aromatic or a heteroaromatic radical optionally substituted, in particular, with an alkyl or a carboxyl group,   R 2  and R 3  represent, in particular, H or alkyl, or   R 2  and R 3 , taken together, form a 5- or 6-membered ring,   R 4  and R 5  represent, in particular, H or halogen,   R 6  represents, in particular, H or lower alkyl,   and the salts of the compounds of formula (I).       
     These compounds can be used in particular in the treatment of dermatological complaints associated with a keratinization disorder, and for combating ageing of the skin.

This application is a division of application Ser. No. 09/932,938, filedAug. 21, 2001 (now U.S. Pat. No. 6,649,612), which is a divisional ofapplication Ser. No. 09/284,026, filed Apr. 6,1999 (now U.S. Pat. No.6,316,009), which is a 371 National Phase of PCT/FR98/01834, filed 21Aug. 1998, the entire content of each of which is hereby incorporated byreference in this application.

The invention relates to, as novel and useful industrial products,biphenyl derivatives substituted with an aromatic or heteroaromaticradical. The invention also relates to the use of these novel compoundsin pharmaceutical compositions intended for use in human or veterinarymedicine, or alternatively in cosmetic compositions.

The compounds according to the invention have pronounced activity in thefields of cell differentiation and proliferation and find applicationsmore particularly in the topical and systemic treatment ofdermatological complaints associated with a keratinization disorder,dermatological (or other) complaints with an inflammatory and/orimmunoallergic component, and dermal or epidermal proliferations,whether they are benign or malignant. These compounds can also be usedin the treatment of connective tissue degenerative diseases, forcontrolling ageing of the skin, whether this is light-induced orchronological ageing, and for treating cicatrization disorders. Theymoreover find an application in the opthalmological field, in particularin the treatment of corneopathy.

The compounds according to the invention can also be used in cosmeticcompositions for body and hair hygiene.

Triaromatic derivatives whose structure consists essentially of twosubstituted aromatic rings linked together by a 5- or 6-memberedheteroaryl divalent radical containing, as hetero atom, an oxygen atom,a sulphur atom and/or at least one nitrogen atom, have already beendescribed in EP-382,077.

The compounds according to the present invention, which are alsotriaromatic derivatives, differ from those of EP-382,077 essentially inthat if they have a heteroaryl radical, in particular a substitutedpyridyl, furyl or thienyl radical, this radical is located at the end ofthe chain, thus giving these compounds a chemical structure which istotally different from that of the compounds of EP-382,077.

Although the compounds according to the invention are not limited tothose containing a heteroaryl radical, it has nevertheless been found,surprisingly and unexpectedly, that the compounds containing such aradical have excellent pharmaceutical and cosmetic properties which areentirely similar to those of the compounds according to the inventioncontaining a substituted phenyl radical at the end of the chain.

It has moreover been possible to demonstrate that the compoundsaccording to the invention are devoid of side effects, while at the sametime having excellent activity.

The subject of the present invention is thus novel compounds which canbe represented by the following general formula:

in which:

-   -   Ar represents an aromatic or heteroaromatic radical chosen from:

-   -   Z being O or S,    -   R₁ represents —CH₃, —CH₂—OH, —OR₈ or —COR₉,    -   R₂ and R₃, which may be identical or different, represent H,        linear or branched C₁–C₁₅ alkyl, cycloalkyl, —ZR₁₀ or a        polyether radical, at least one from among R₂ and R₃        representing a linear or branched C₁–C₁₅ alkyl, or    -   R₂ and R₃, taken together, form a 5- or 6-membered ring,        optionally sutbstituted with at least one methyl and/or        optionally interrupted by an oxygen or sulphur atom or by an SO        or SO₂ radical,    -   R₄ represents H, a halogen atom, linear or branched C₁–C₂₀        alkyl, —OR₁₀, —OCOR₁₁ or a polyether radical,    -   R₅ represents H, a halogen atom, linear or branched C₁–C₂₀        alkyl, —OCOR₁₁, —OR₁₂, mono- or polyhydroxyalkyl, —NO₂,

-   -    —(CH₂)_(n)—NHCOCH₃, —CH═CH—COR₁₃, —(CH₂)_(n)COR₁₃, n being 0 to        6, —O—(CH₂)_(m)COR₁₃, —O—(CH₂)_(m)OH, m being 1 to 12,        optionally substituted aryl, optionally substituted aralkyl,        optionally substituted heteroaryl, a polyether radical or a        —CH₂-polyether radical,    -   R₆ represents H, lower alkyl or —OR₁₀,        -   R₇ represents H, a halogen atom, linear or branched C₁–C₂₀            alkyl, —OR₁₀ or —OCOR₁₁ or a polyether radical,    -   R₈ represents H, lower alkyl or —COR₁₁,    -   R₉ represents H, lower alkyl, —OR₁₄ or

-   -   R₁₀ represents H or lower alkyl,    -   R₁₁ represents lower alkyl,    -   R₁₂ represents H, linear or branched C₁–C₂₀ alkyl, mono- or        polyhydroxyalkyl, or optionally substituted aryl or aralkyl,    -   R₁₃ represents H, lower alkyl, —OR₁₀, aryl or

-   -   R₁₄ represents H, alkyl, linear or branched C₁–C₂₀ alkyl,        alkenyl, mono- or polyhydroxyalkyl, optionally substituted aryl        or aralkyl, or a sugar residue,    -   r′ and r″, which may be identical or different, represent H, OH,        lower alkyl, mono- or polyhydroxyalkyl, optionally substituted        aryl, an amino acid residue or a peptide residue, or r′ and r″,        taken together, form a heterocycle,    -   and the salts of the compounds of formula (I) when R₁ represents        a carboxylic acid function, as well as the optical and        geometrical isomers of the said compounds of formula (I).

When the compounds according to the invention are in the form of a salt,this is preferably a salt of an alkali metal or alkaline-earth metal, oralternatively of zinc or of an organic amine.

According to the present invention, the expression “lower alkyl” refersto a C₁–C₆ radical, preferably the methyl, ethyl, isopropyl, butyl,tert-butyl and hexyl radicals.

The term “linear or branched C₁–C₁₅ alkyl” refers in particular to themethyl, ethyl, propyl, 2-ethylhexyl, octyl and dodecyl radicals. Whenthe alkyl radical is C₁–C₂₀, the hexadecyl and octadecyl radicals arealso intended.

The term “cycloalkyl” refers to an optionally substituted mono- orpolycyclic radical containing from 5 to 10 carbon atoms, in particular acyclopentyl, cyclohexyl, 1-methylcyclohexyl or 1-adamantyl radical.

The term “monohydroxyalkyl” refers to a radical preferably containing 1to 6 carbon atoms, in particular a hydroxymethyl, 2-hydroxyethyl,2-hydroxypropyl or 3-hydroxypropyl radical.

The term “polyhydroxyalkyl” refers to a radical preferably containing 3to 6 carbon atoms and from 2 to 5 hydroxyl groups, such as the2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl and2,3,4,5-tetrahydroxypentyl radicals or a pentaerythritol residue.

The term “polyether radical” refers to a radical containing from 2 to 6carbon atoms which is interrupted by at least two oxygen atoms, such asthe methoxymethoxy, methoxyethoxy and methoxyethoxymethoxy radicals.

The term “—CH₂-polyether radical” refers to a radical preferably chosenfrom the methoxymethoxymethyl, ethoxymethoxymethyl andmethoxyethaxymethoxymethyl radicals.

The term “aryl” preferably refers to a phenyl radical optionallysubstituted with at least one halogen, a lower alkyl, a hydroxyl, aC₁–C₃ alkoxy, a nitro function, a polyether radical or an amino functionoptionally protected with an acetyl group or optionally substituted withat least one C₁–C₆ lower alkyl or alkoxy.

The term “aralkyl” preferably refers to a benzyl or phenethyl radicaloptionally substituted with at least one halogen, a lower alkyl, ahydroxyl, a C₁–C₃ alkoxy, a nitro function, a polyether radical or anamino function optionally protected with an acetyl group or optionallysubstituted with at least one C₁–C₆ lower alkyl or alkoxy.

The term “heteroaryl radical” preferably refers to a pyridyl, furyl orthienyl radical, optionally substituted with at least one halogen, alower alkyl, a hydroxyl, a C₁–C₃ alkoxy, a nitro function, a polyetherradical or an amino function optionally protected with an acetyl groupor optionally substituted with at least one C₁–C₆ lower alkyl or alkoxy.

The term “alkenyl” refers to a radical preferably containing 2 to 5carbon atoms and containing one or more ethylenic unsaturations, suchas, more particularly, an allyl radical.

The term “sugar residue” refers to a residue derived in particular fromglucose, from galactose or from mannose, or alternatively fromglucuronic acid.

The term “amino acid residue” refers in particular to a residue derivedfrom lysine, from glycine or from aspartic acid, and the term “peptideresidue” refers more particularly to a dipeptide or tripeptide residueresulting from the combination of amino acids.

The term “heterocycle” preferably refers to a piperidino, morpholino,pyrrolidono or piperazino radical, optionally substituted in position 4with a C₁–C₆ lower alkyl or a mono- or polyhydroxyalkyl as definedabove.

When R₄, R₅ and/or R₇ represent a halogen atom, this is preferably afluorine, chlorine or bromine atom.

According to a preferred embodiment, the compounds according to theinvention correspond to the general formulae (II) and (III) below:

in which:

-   -   Ar represents a radical of formula (a) or (b) below:

-   -   R₁, R₄, R₅, R₆, R₇ and Z having the same meanings as those given        above for formula (I),    -   R₁₅, R₁₆, R₁₇ and R₁₈, which may be identical or different,        represent H or —CH₃, and    -   t is 1 or 2.

Among the compounds of formulae (I) to (III) above, according to thepresent invention, mention may be made in particular of the following:

-   4-[4-hydroxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid, and its methyl ester,-   4-[4-(5-hydroxypentyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid, and its methyl ester,-   4-[4-(6-hydroxyhexyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid and its methyl ester,-   4-[4-(7-hydroxyheptyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid,-   4-[4-(8-hydroxyoctyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid,-   4-[4-(9-hydroxynonyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid,-   4-[4-methoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid,-   4-[4-methoxyethoxymethoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid,-   4-[4-benzyloxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoic    acid,-   4′-(2,3-dihydroxypropoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid (racemic),-   4′-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-biphenyl-4-carboxylic    acid (racemic),-   4′-(2-morpholin-4-yl-ethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   methyl    2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate,-   2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   4-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   4-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   4-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   3-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   3-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   3-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-methoxymethoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-methoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-propyloxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-hydroxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   4′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;2′,1″]terphenyl-4″-carboxylic    acid,-   2′-methoxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-hydroxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-methoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   3′-methoxymethoxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   3′-hydroxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-(4,4-dimethylthiochroman-7-yl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(4,4-dimethylthiochroman-6-yl)-[1,1′;4′,1″]terphenyl-41-carboxylic    acid,-   2′-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(3-methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(3-methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(3-propyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   3″-methyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2″-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2″-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2″-propyloxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   3″-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   6-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]nicotinic    acid,-   5-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-2-pyridinecarboxylic    acid,-   2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-hydroxamic    acid,-   2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-ol,-   [2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-yl]methanol,-   2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carbaldehyde,-   4′-methoxycarbonylmethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   4′-carboxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   4′-(5-ethoxycarbonylpentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   4′-(5-carboxypentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide,-   N-ethyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide,-   N,N-diethyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide,-   morpholin-4-yl-[2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″l]terphenyl-4″-yl]methanone,-   (4-hydroxyphenyl)-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-40-carboxamide,-   3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxymethyl-4′-carboxylic    acid,-   3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4,4′-dicarboxylic    acid,-   3′-methoxymethoxy-51-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   3′-methoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   3′-propyloxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   3′-hydroxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   4′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;3′,1″]terphenyl-4″-carboxylic    acid,-   4′-(5-carboxamidopentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   3′-methoxycarbonyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   3′-carboxyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylic    acid,-   2′-(4-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(4-methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(4-propyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2′-(4-methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic    acid,-   2-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-4-thiophenecarboxylic    acid.

A subject of the present invention is also the processes for preparingthe compounds of formula (I) above according to the reaction schemesgiven in Tables A and B.

With reference to Table A, the compounds of formula (Ia) can be obtainedby a Suzuki-type coupling reaction between a boronic derivative offormula (6) and a biaromatic bromo derivative of formula (7). Theboronic derivative of formula (6) is obtained from the halo derivativeof formula (5), preferably the bromo or iodo derivative. The biaromaticbromo derivative of formula (7) can be obtained by two different routesinvolving a Suzuki-type coupling reaction. The first consists inreacting a haloaromatic compound of formula (1) with a bromoboronicderivative of formula (2) and the second consists in reacting anaromatic boronic derivative of formula (3) with an idobromoaromaticderivative of formula (4).

The reaction conditions for these various steps are essentiallydescribed in:

-   -   N. Miyaura, Synthetic Communications 1981, 11(7), 513–9,    -   A. Suzuki, Synlett 1990, 221,    -   A. R. Martin, Acta Chemica Scandinavia 1993, 47, 221–30,    -   G. Marck, Tetrahedron Letters 1994, vol. 35, No. 20, 3277–80,    -   T. Wallow, J. Org. Chem. 1994, 59, 5034–7,    -   H. Zhang, Tetrahedron Letters 1996, vol. 37, No. 7, 1043–4.

The boronic derivatives of formulae (2), (3) and (6) can be preparedaccording to the following two methods:

(a) either by reaction with butyllithium and then with an alkyl borate,preferably triisopropyl borate or trimethyl borate, followed byhydrolysis with hydrochloric acid,

(b) or by reaction with the pinacol ester of the diboronic acidaccording to the method described by T. Ishiyama, J. Org. Chem. 1995,60, 7508–10.

Starting with the compound of formula (Ia), it is possible to gainaccess to the compounds of formulae (Ib) and (Ic).

The compounds of formula (Ib) can be obtained from the compounds offormula (Ia) (R₅═OH) by reaction of a halo derivative (9) in thepresence of a solvent such as acetone, methyl ketone [sic] or DMF and abase such as potassium carbonate or sodium hydride.

The compounds of formula (Ic) can be obtained from the compounds offormula (Ia) (R₅═OH) by standard acylation reaction starting with anacid (10).

The compounds of formula (Id) can be obtained from compounds of formula(Ia) (R₅═OH) which are converted, in a first step, into triflatederivatives of formula (8) and then, in a second step, are reactedeither under Suzuki-type reaction conditions with an aromatic boronicderivative (12), or under Stille-type reaction conditions with anaromatic stannic derivative (11) according to the method described by A.M. Echavarren, J. Am. Chem. Soc. 1987, 109, 5478–86.

Referring now to Table B, the compounds of formulae (Ie), (If) and (Ig)can be obtained directly from triflate derivatives of formula (8) bycarbonylation in the presence of a palladium catalyst and using,respectively, an alcoholic derivative, an amine or a trialkylsilane,according to the methods described by J. K. Stille, Angew Chem. Int.,Ed. Engl. 1996, 508–524 and H. Kotsuki, Synthesis 1996, 470–2.

The compounds of formula (Ih) can also be obtained from triflatederivatives of formula (8) by reaction with an acrylic ester (13) in thepresence of a palladium catalyst, according to the method described inJ. Med. Chem. 1990, vol. 33, No. 7, 1919–24. Starting with theunsaturated compound of formula (Ih), it is possible to gain accessdirectly, by catalytic hydrogenation, to the compound of formula (Ii).

The compounds of formula (Ij) can again be obtained from triflatederivatives of formula (8) by reaction with stannic derivatives such asvinyltributyltin or allyltributyltin (14) in the presence of a palladiumcatalyst. The intermediate compound obtained of formula (15) is thensubjected to an oxidation reaction with osmium tetroxide, under theconditions described in J. Org. Chem. 1990, vol. 55, No. 3, 906–9 and J.Med. Chem. 1991, vol. 34, No. 5, 1614–23.

When, in the compounds of formula (I) according to the invention, R₁represents a —COOH radical, these are prepared according to twodifferent synthetic routes:

(a) The first consists in protecting the carboxylic acid function with aprotecting group of alkyl, allyl, benzyl or tert-butyl type.

When the protecting group is an alkyl, the deprotection is obtainedusing sodium hydroxide or lithium hydroxide in an alcoholic solvent suchas methanol, or THF.

When the protecting group is an allyl radical, the deprotection iscarried out using a catalyst such as certain transition metal complexes,in the presence of a secondary amine such as morpholine.

When the protecting group is a benzyl radical, the deprotection iscarried out in the presence of hydrogen using a catalyst such aspalladium on charcoal.

Lastly, when the protecting group is a tert-butyl radical, thedeprotection is carried out using trimethylsilane [sic] iodide.

(b) The second consists in starting with the corresponding phenoliccompound, which is converted into the triflate, and is then subjected toa carbonylation in the presence of a palladium catalyst.

When, in the compounds of formula (I) according to the invention, R₁represents an alcohol function, these can be obtained:

(a) either from the corresponding aldehyde derivatives by the action ofan alkali metal hydride such as sodium borohydride, in an alcoholicsolvent such as methanol,

(b) or starting with the acid derivatives of formula (Ie) (R₁₀═H) byreduction with lithium aluminium hydride.

When, in the compounds of formula (I) according to the invention, R₁represents an aldehyde function, these can be obtained by oxidation ofthe corresponding alcohols in the presence of manganese oxide,pyridinium dichromate or the Swern reagent.

Lastly, when, in the compounds of formula (I) according to theinvention, R₁ represents an amide function, these can be obtained byreaction of the acid chlorides, obtained from the correspondingcarboxylic acids, with aliphatic, aromatic or heterocyclic amines in thepresence of dicyclohexylcarbodiimide or carbonyldiimidazole.

A subject of the present invention is also the compounds of formula (I)as defined above, as medicinal products.

These compounds have agonist or antagonist activity with respect to theexpression of one or more biological markers in the test ofdifferentiation of mouse embryonic teratocarcinoma cells (F9) (SkinPharmacol. 3, p. 256–267, 1990) and/or on the in vitro differentiationof human keratinocytes (Skin Pharmacol. 3, p. 70–85, 1990). Theseabovementioned tests show the activities of the compounds in the fieldsof differentiation and proliferation. The activities can also bemeasured in cellular transactivation tests using RAR recombinantreceptors according to the method by B. A. Bernard et al., Biochemicaland Biophysical Research Communication, 1992, vol. 186, 977–983.

The compounds according to the invention are particularly suitable inthe following fields of treatment:

-   1) for treating dermatological complaints associated with a    keratinization disorder which has a bearing on differentiation and    on proliferation, in particular for treating common acne, comedones,    polymorphonuclear leukocytes, rosacea, nodulocystic acne, acne    conglobata, senile acne and secondary acne such as solar,    medication-related or occupational acne,-   2) for treating other types of keratinization disorder, in    particular ichthyosis, ichthyosiform states, Darier's disease,    palmoplantar keratoderma, leucoplasias and leucoplasiform states,    and cutaneous or mucous (buccal) lichen,-   3) for treating other dermatological complaints associated with a    keratinization disorder with an inflammatory and/or immunoallergic    component and, in particular, all forms of psoriasis, whether it is    cutaneous, mucous or ungual psoriasis and even psoriatic rheumatism,    or alternatively cutaneous atopy, such as eczema or respiratory    atopy or alternatively gingival hypertrophy; the compounds can also    be used in certain inflammatory complaints which have no    keratinization disorder;-   4) for treating all dermal or epidermal proliferations, whether    benign or malignant and whether they are of viral origin or    otherwise, such as common warts, flat warts and verruciform    epidermodysplasia, it being also possible for the oral or florid    papillomatoses and the proliferations to be induced by ultraviolet    radiation, in particular in the case of basocellular and    spinocellular epithelioma,-   5) for treating other dermatological disorders such as bullosis and    collagen diseases,-   6) for treating certain ophthalmological disorders, in particular    corneopathies,-   7) for repairing or combating ageing of the skin, whether this is    light-induced or chronological ageing, or for reducing actinic    keratoses and pigmentations, or any pathologies associated with    chronological or actinic ageing,-   8) for preventing or curing the stigmata of epidermal and/or dermal    atrophy induced by local or systemic corticosteroids, or any other    form of cutaneous atrophy,-   9) for preventing or treating cicatrization disorders or for    preventing or repairing stretch marks,-   10) for combating disorders of sebaceous functioning such as the    hyperseborrhoea of acne or simple seborrhoea,-   11) in the treatment or prevention of cancerous or precancerous    states,-   12) in the treatment of inflammatory complaints such as arthritis,-   13) in the treatment of any general or skin complaint of viral    origin,-   14) in the prevention or treatment of alopecia,-   15) in the treatment of dermatological or general complaints having    an immunological component,-   16) in the treatment of complaints of the cardiovascular system such    as arteriosclerosis.

In the therapeutic fields mentioned above, the compounds according tothe invention may be employed advantageously in combination with othercompounds of retinoid-type activity, with D vitamins or derivativesthereof, with corticosteroids, with anti-free-radical agents, α-hydroxyor α-keto acids or derivatives thereof, or alternatively withion-channel blockers. The expression “D vitamins or derivatives thereof”means, for example, vitamin D₂ or D₃ derivatives and in particular1,25-dihydroxyvitamin D₃. The expression “anti-free-radical agents”means, for example, α-tocopherol, superoxide dismutase or SOD, ubiquinolor certain metal-chelating agents. The expression “α-hydroxy or α-ketoacids or derivatives thereof” means, for example, lactic, malic, citric,glycolic, mandelic, tartaric, glyceric or ascorbic acid or the salts,amides or esters thereof. Lastly, the term “ion-channel blockers” means,for example, Minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxide) andderivatives thereof.

A subject of the present invention is also pharmaceutical compositionscontaining at least one compound of formula (I) as defined above, one ofthe optical or geometrical isomers thereof or one of the salts thereof.

The pharmaceutical compositions intended in particular for treating theabovementioned complaints, and are characterized in that they comprise apharmaceutically acceptable support which is compatible with the mode ofadministration selected, at least one compound of formula (I), one ofthe optical or geometrical isomers thereof or one of the salts thereof.

The compounds according to the invention may be administered enterally,parenterally, topically or ocularly.

Via the enteral route, the compositions may be in the form of tablets,gelatin capsules, sugar-coated tablets, syrups, suspensions, solutions,powders, granules, emulsions, microspheres or nanospheres or polymericor lipid vesicles which enable controlled release. Via the parenteralroute, the compositions may be in the form of solutions or suspensionsfor infusion or for injection.

The compounds according to the invention are generally administered at adaily dose of about 0.01 mg/kg to 100 mg/kg of body weight taken in 1 to3 doses.

Via the topical route, the pharmaceutical compositions based oncompounds according to the invention are more particularly intended forthe treatment of the skin and the mucosae and may be in the form ofointments, creams, milks, salves, powders, impregnated pads, solutions,gels, sprays, lotions or suspensions. They may also be in the form ofmicrospheres or nanospheres or polymeric or lipid vesicles or polymericpatches and hydrogels which enable controlled release of the activeprinciple. Furthermore, these topical-route compositions may either bein anhydrous form or in aqueous form, depending on the clinicalindication.

Via the ocular route, they are mainly eyedrops.

These compositions for topical or ocular use contain at least onecompound of formula (I) as defined above, or one of the optical orgeometrical isomers thereof or alternatively one of the salts thereof,at a concentration preferably of between 0.001% and 5% by weightrelative to the total weight of the composition.

The compounds of formula (I) according to the invention also find anapplication in the cosmetic field, in particular in body and hairhygiene and especially for treating skin types with a tendency towardsacne, for promoting the regrowth of the hair, for combating hair loss,for combating the greasy appearance of the skin or the hair, inprotection against the harmful effects of the sun or in the treatment ofphysiologically dry skin types, and for preventing and/or combatinglight-induced or chronological ageing.

In the cosmetic field, the compounds according to the invention canmoreover be employed advantageously in combination with other compoundsof retinoid-type activity, with D vitamins or derivatives thereof, withcorticosteroids, with anti-free-radical agents, α-hydroxy or α-ketoacids or derivatives thereof, or alternatively with ion-channelblockers, all of these various products being as defined above.

The present invention is thus also directed towards a cosmeticcomposition which is characterized in that it comprises, in acosmetically acceptable support, at least one compound of formula (I) asdefined above or one of the optical or geometrical isomers thereof orone of the salts thereof, it being possible for the said cosmeticcomposition to be, in particular, in the form of a cream, a milk, alotion, a gel, microspheres or nanospheres or polymeric or lipidvesicles, a soap or a shampoo.

The concentration of compound of formula (I) in the cosmeticcompositions according to the invention is advantageously between 0.001%and 3% by weight relative to the entire composition.

The pharmaceutical and cosmetic compositions according to the inventioncan also contain inert additives or even pharmacodynamically orcosmetically active additives or combinations of these additives and, inparticular: wetting agents; depigmenting agents such as hydroquinone,azelaic acid, caffeic acid or kojic acid; emollients; moisturizingagents such as glycerol, PEG-400, thiamorpholinone and derivativesthereof, or urea; anti-seborrhoea or anti-acne agents such asS-carboxymethylcysteine, S-benzylcysteamine, the salts or derivativesthereof, or benzoyl peroxide; antibiotics such as erythromycin andesters thereof, neomycin, clindamycin and esters thereof, andtetra-cyclines; antifungal agents such as ketoconazole or4,5-polymethylene-3-isothiazolidones; agents for promoting the regrowthof the hair, such as Minoxidil(2,4-diamino-6-piperidinopyrimidine-3-oxide) and derivatives thereof,Diazoxide (7-chloro-3-methyl-1,2,4-benzo-thiadiazine 1,1-dioxide) andPhenytoin (5,4-diphenyl-imidazolidine-2,4-dione); non-steroidalanti-inflammatory agents; carotenoids and, in particular, β-carotene;anti-psoriatic agents such as anthraline and derivatives thereof and,lastly, eicosa-5,8,11,14-tetraynoic acid and eicosa-5,8,11-triynoicacid, the esters and amides thereof.

The compositions according to the invention may also containflavour-enhancing agents, preserving agents such as para-hydroxybenzoicacid esters, stabilizing agents, moisture regulators, pH regulators,osmotic pressure modifiers, emulsifying agents, UV-A and UV-B screeningagents, and antioxidants such as α-tocopherol, butylated hydroxyanisoleor butylated hydroxytoluene.

Several examples for obtaining the active compounds of formula (I)according to the invention, as well as various cosmetic andpharmaceutical formulations based on such compounds, will now be givenfor illustrative purposes and with no limiting nature.

EXAMPLES Example 14-[4-Hydroxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) 5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthylboronic acid

21.38 g (80.0 mmol) of5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-bromonaphthalene and 50 ml ofTHF are introduced into a three-necked flask under a stream of nitrogen.38.4 ml (96.0 mmol) of n-butyllithium (2.5 M in hexane) are addeddropwise, at −78° C., and the mixture is stirred for one hour. 27.7 ml(120.0 mmol) of triisopropyl borate are added dropwise at this sametemperature and the mixture is stirred for 2 hours. 350 ml ofhydrochloric acid (1 N) are added at −50° C. and the mixture is allowedto warm to room temperature. The reaction medium is extracted withdichloromethane and the organic phase is separated out after settlinghas taken place, dried over magnesium sulphate and evaporated. 18.60 g(100%) of the expected boronic acid are collected in the form of an oilwhich crystallizes slowly. Melting point 190–192° C.

¹H NMR (CDCl₃) δ 1.34 (s, 6H), 1.39 (s, 6H), 1.75 (s, 4H), 4.88 (s, 2H),7.47 (d, 1H, J=7.9 Hz), 7.97 (d, 1H, J=7.9 Hz), 8.21 (s, 1H).

(b) Methyl (or ethyl) 4-(4-hydroxyphenyl)benzoate

10.10 g (47.3 mmol) of 4-(4-hydroxyphenyl)-benzoic acid and 150 ml ofmethanol (or of ethanol) are introduced into a round-bottomed flask and2.5 ml of concentrated sulphuric acid are added dropwise. The reactionmedium is refluxed for twelve hours and evaporated to dryness. Theresidue obtained is taken up in a mixture of water and ethyl ether andthe organic phase is separated out after settling has taken place,washed with water, dried over magnesium sulphate and evaporated. 10.60 g(98%) of the expected ester are obtained in the form of a colourlessoil.

¹H NMR (methyl ester) (CDCl₃) δ 3.87 (s, 3H), 6.90 (d, 2H, J=8.5 Hz),7.59 (d, 2H, J=8.6 Hz), 7.74 (d, 2H, J=8.4 Hz), 7.99 (d, 2H, J=8.4 Hz),9.77 (s, 1H).

(c) Methyl (or Ethyl) 4-(3-bromo-4-hydroxyphenyl)-benzoate

9.35 g (41.0 mmol) of methyl (or ethyl) 4-(4-hydroxyphenyl)benzoate, 125ml of dioxane and 40 ml of THF are introduced into a round-bottomedflask. 12.19 g (49.1 mmol) of Br₂/dioxane complex are added and themixture is stirred for 24 hours at room temperature. The reaction mediumis evaporated to dryness, the residue is taken up in water and ethylacetate and the organic phase is separated out after settling has takenplace, dried over magnesium sulphate and evaporated. The residueobtained is purified by chromatography on a column of silica, elutedwith a mixture of ethyl acetate and heptane (20/80). After evaporationof the solvents, 10.80 g (86%) of the expected product are collected inthe form of white crystals with a melting point of 145–146° C. (methylester).

¹H NMR (methyl ester) (CDCl₃) δ 3.94 (s, 3H), 5.74 (s, 1H), 7.11 (d, 1H,J=8.5 Hz), 7.49 (dd, 1H, J=8.5/2.1 Hz), 7.58 (d, 2H, J=8.5 Hz), 7.74 (d,1H, J=2.1 Hz), 8.08 (d, 2H, J=8.5 Hz).

(d) Methyl (or Ethyl)4-[4-hydroxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

11.41 g (49.1 mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylboronic acid, 0.06 g (32.7 mmol) of methyl (or ethyl)4-(3-bromo-4-hydroxyphenyl)benzoate, 640 ml of toluene and 39.3 ml (78.6mmol) of potassium carbonate solution (2M) are introduced into athree-necked flask. The reaction medium is degassed by bubbling nitrogenthrough, 69 mg (0.06 mmol) of tetrakistriphenylphosphinepalladium(0) areadded and the mixture is heated at 90° C. for twenty hours. The reactionmedium is evaporated to dryness and the residue is taken up in water andethyl ether and acidified. The organic phase is separated out aftersettling has taken place, dried over magnesium sulphate and evaporated.The residue obtained is purified by chromatography on a column of silicaeluted with dichloromethane. 11.57 g (85%) of the expected product arecollected in the form of a very pale yellow solid with a melting pointof 178–181° C. (methyl ester).

¹H NMR (methyl ester) (CDCl₃) δ 1.32 (s, 6H), 1.33 (s, 6H), 1.73 (s,4H), 3.93 (s, 3H), 5.52 (s, 1H), 7.09 (d, 1H, J=9.1 Hz), 7.26 (dd, 1H,J=7.1/1.9 Hz), 7.42 to 7.44 (m, 2H), 7.47 to 7.55 (m, 2H), 7.64 (d, 2H,J=8.4 Hz), 8.08 (d, 2H, J=8.4 Hz).

(e)4-[4-Hydroxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

1.24 g (3.0 mmol) of the methyl (or ethyl) ester obtained in Example1(d) and 7.5 ml of methanolic sodium hydroxide (4N) are introduced intoa round-bottomed flask. The reaction medium is refluxed for four hours,poured into water, acidified and extracted with ethyl ether, and theorganic phase is separated out after settling has taken place, driedover magnesium sulphate and evaporated. The residue obtained ischromatographed on a short column of silica, eluted with ethyl ether.1.00 g (83%) of4-[4-hydroxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-phenyl]benzoicacid is obtained in the form of white crystals with a melting point of240–241° C.

¹H NMR (CDCl₃) δ 1.33 (s, 6H), 1.34 (s, 6H), 1.74 (s, 4H), 7.10 (d, 1H,J=8.7 Hz), 7.26 (dd, 1H, J=7.2/1.8 Hz), 7.42 to 7.48 (m, 2H), 7.54 to7.58 (m, 2H), 7.69 (d, 2H, J=8.4 Hz), 8.16 (d, 2H, J=8.4 Hz).

Example 24-[4-(5-Hydroxypentyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) Methyl4-[4-(5-acetoxypentyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

1.66 g (4.0 mmol) of the methyl ester obtained in Example 1(d), 150 mlof acetone and 2.21 g (16.0 mmol) of potassium carbonate are introducedinto a round-bottomed flask. 2.67 ml (16.0 mmol) of 5-bromo-pentylacetate are added and the mixture is refluxed for eight hours. Thereaction medium is evaporated to dryness, the residue is taken up inethyl acetate and water and the organic phase is separated out aftersettling has taken place, dried over magnesium sulphate and evaporated.2.20 g (100%) of the expected product are collected in the form of acolourless oil.

¹H NMR (CDCl₃) δ 1.32 (s, 12H), 1.66 (s, 4H), 1.45 to 2.05 (m, 6H), 3.41(t, 2H, J=6.7 Hz), 3.93 (s, 3H), 4.04 (t, 2H, J=6.7 Hz), 7.04 (d, 1H,J=8.5 Hz), 7.29 to 7.38 (m, 2H), 7.52 to 7.58 (m, 2H), 7.62 (d, 1H,J=2.4 Hz), 7.66 (d, 2H, J=8.4 Hz), 7.87 (d, 2H, J=8.3 Hz).

(b)4-[4-(5-Hydroxypentyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 2.20 g (4.0mmol) of the methyl ester obtained in Example 2(a), and after taking upin an ethyl ether/hexane mixture (10/90) and filtration, 1.45 g (74%) of4-[4-(5-hydroxypentyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]-benzoicacid are obtained in the form of a white solid with a melting point of195–196° C.

¹H NMR (CDCl₃) δ 1.32 (s, 12H), 1.49 to 1.61 (m, 3H), 1.72 (s, 4H), 1.77to 1.85 (m, 3H), 3.59 (t, 2H, J=6.1 Hz), 4.03 (t, 2H, J=6.4 Hz), 7.04(d, 1H, J=8.6 Hz), 7.30 to 7.38 (m, 2H), 7.54 (dd, 1H, J=8.5/2.2 Hz),7.58 to 7.62 (m, 2H), 7.65 (d, 2H, J=8.4 Hz), 8.10 (d, 2H, J=8.3 Hz).

Example 34-[4-(6-Hydroxyhexyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) Methyl4-[4-(6-hydroxyhexyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 2(a), by reaction of 1.66 g ofthe methyl ester obtained in Example 1(d) with 2.1 ml (16.0 mmol) of6-bromohexanol, 2.10 g (100%) of the expected product are obtained inthe form of a colourless oil.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.41 to 1.93 (m, 8H), 1.72 (s, 4H), 3.65(t, 2H, J=6.3 Hz), 3.93 (s, 3H), 4.02 (t, 2H, J=6.4 Hz), 7.04 (d, 1H,J=8.5 Hz), 7.30 to 7.38 (m, 2H), 7.54 (dd, 1H, J=8.5/2.3 Hz), 7.59 to7.62 (m, 2H), 7.66 (d, 2H, J=8.4 Hz), 8.08 (d, 2H, J=8.3 Hz).

(b)4-[4-(6-Hydroxyhexyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 2.10 g (4.0mmol) of the methyl ester obtained in Example 3(a), 1.70 g (86%) of4-[4-(6-hydroxyhexyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid are obtained in the form of a white solid With a melting point of200–201° C.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.38 to 1.83 (m, 8H), 1.72 (s, 4H), 3.59(t, 2H, J=6.4 Hz), 4.03 (t, 2H, J=6.5 Hz), 7.04 (d, 1H, J=8.6 Hz), 7.30to 7.38 (m, 2H), 7.54 (dd, 1H, J=8.5/2.3 Hz), 7.60 to 7.62 (m, 2H), 7.65(d, 2H, J=8.4 Hz), 8.10 (d, 2H, J=8.4 Hz).

Example 44-[4-(7-Hydroxyheptyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) Ethyl4-[4-(7-hydroxyheptyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 2(a), by reaction of 1.50 g (3.5mmol) of the ethyl ester obtained in Example 1(d) with 1.06 g (5.4 mmol)of 7-bromoheptanol, 1.43 g (75%) of the expected product are obtained inthe form of a colourless oil.

¹H NMR (CDCl₃) δ 1.18 to 1.24 (m, 2H), 1.33 (s, 12H), 1.41 (t, 3H, J=7.1Hz), 1.52 to 1.58 (m, 4H), 1.72 (s, 4H), 1.72 to 1.82 (m, 4H), 3.60 to3.64 (m, 2H), 4.02 (t, 2H, J=6.5 Hz), 4.39 (q, 2H, J=7.1 Hz), 7.04 (d,1H, J=8.5 Hz), 7.32 to 7.38 (m, 2H), 7.54 (dd, 1H, J=8.4/2.4 Hz), 7.59to 7.63 (m, 2H), 7.65 (d, 2H, J=8.5 Hz), 8.09 (d, 2H, J=8.4 Hz).

(b)4-[4-(7-Hydroxyheptyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 1.40 g (2.6mmol) of the ethyl ester obtained in Example 4(a), 1.15 g (87%) of4-[4-(7-hydroxyheptyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid are obtained in the form of a white solid with a melting point of168–172° C.

¹H NMR (CDCl₃) δ 1.21 to 1.43 (m, 6H), 1.33 (s, 12H), 1.53 to 1.56 (m,2H), 1.73 (s, 4H), 1.77 to 1.82 (m, 2H), 3.64 (t, 2H, J=6.5 Hz), 4.02(t, 2H, J=6.5 Hz), 7.05 (d, 1H, J=8.6 Hz), 7.31 to 7.38 (m, 2H), 7.55(dd, 1H, J=8.5/2.4 Hz), 7.59 (s, 1H), 7.64 (d, 1H, J=2.4 Hz), 7.69 (d,2H, J=8.4 Hz), 8.16 (d, 2H, J=8.4 Hz)

Example 54-[4-(8-Hydroxyoctyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) Methyl4-[4-(8-hydroxyoctyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 2(a), by reaction of 700 mg (1.7mmol) of the methyl ester obtained in Example 1(d) with 1.15 ml (6.7mmol) of 8-bromooctanol, 920 mg (100%) of the expected product areobtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.38 to 1.83 (m, 12H), 1.72 (s, 4H),3.64 (t, 2H, J=6.5 Hz), 3.93 (s, 3H), 4.02 (t, 2H, J=6.5 Hz), 7.05 (d,1H, J=8.6 Hz), 7.52 to 7.67 (m, 4H), 7.69 (d, 2H, J=8.3 Hz), 8.15 (d,2H, J=8.3 Hz).

(b)4-[4-(8-Hydroxyoctyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 920 mg (1.7mmol) of the methyl ester obtained in Example 5(a), 740 mg (83%) of4-[4-(8-hydroxyoctyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid are obtained in in the form of pale yellow crystals with a meltingpoint of 155–160° C.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.38 to 1.83 (m, 12H), 1.72 (s, 4H),3.64 (t, 2H, J=6.5 Hz), 4.03 (t, 2H, J=6.5 Hz), 7.05 (d, 1H, J=8.6 Hz),7.52 to 7.67 (m, 4H), 7.69 (d, 2H, J=8.3 Hz), 8.15 (d, 2H, J=8.3 Hz).

Example 64-[4-(9-Hydroxynonyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) Methyl4-[4-(9-hydroxynonyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 2(a), by reaction of 680 mg (1.6mmol) of the methyl ester obtained in Example 1(d) with 1.47 g (6.6mmol) of 9-bromononanol, 920 mg (100%) of the expected product areobtained in the form of a brown oil.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.38 to 1.83 (m, 14H), 1.72 (s, 4H),3.64 (t, 2H, J=6.5 Hz), 3.93 (s, 3H), 4.02 (t, 2H, J=6.5 Hz), 7.05 (d,1H, J=8.6 Hz), 7.52 to 7.67 (m, 4H), 7.69 (d, 2H, J=8.3 Hz), 8.15 (d,2H, J=8.3 Hz).

(b)4-[4-(9-Hydroxynonyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 920 mg (1.6mmol) of the methyl ester obtained in Example 6(a), 720 mg (81%) of4-[4-(9-hydroxynonyloxy)-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid are obtained in the form of pale yellow crystals with a meltingpoint of 147–150° C.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.38 to 1.83 (m, 14H), 1.72 (s, 4H),3.64 (t, 2H, J=6.5 Hz), 4.03 (t, 2H, J=6.5 Hz), 7.05 (d, 1H, J=8.6 Hz),7.52 to 7.67 (m, 4H), 7.69 (d, 2H, J=8.3 Hz), 8.15 (d, 2H, J=8.3 Hz).

Example 74-[4-Methoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) Methyl4-[4-methoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

1.66 g (4.0 mmol) of the methyl ester obtained in Example 1(d) and 25 mlof DMF are introduced into a reactor under a stream of nitrogen. 144 mg(4.8 mmol) of sodium hydride (80% in oil) are introduced portionwise andthe mixture is stirred until the evolution of gas has ceased. 311 μl(5.0 mmol) of iodomethane are then added and the mixture is stirred fortwo hours. The reaction medium is poured into water and extracted withethyl ether, and the organic phase is separated out after settling hastaken place, dried over magnesium sulphate and evaporated. The residueobtained is purified by chromatography on a column of silica eluted withdichloromethane. After evaporation of the solvents, 1.70 g (100%) of theexpected product are collected in the form of a white crystalline solid.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.72 (s, 4H), 3.87 (s, 3H), 3.93 (s,3H), 7.06 (d, 1H, J=8.4 Hz), 7.36 (s, 2H), 7.52 to 7.61 (m, 3H), 7.66(d, 2H, J=8.3 Hz), 8.09 (d, 2H, J=8.3 Hz).

(b)4-[4-Methoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 1.70 g (4.0mmol) of the methyl ester obtained in Example 7(a), 1.35 g (81%) of4-[4-methoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-phenyl]benzoicacid with a melting point of 251–255° C. are obtained.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.72 (s, 4H), 3.88 (s, 3H), 7.08 (d, 1H,J=8.4 Hz), 7.37 (s, 2H), 7.53 to 7.62 (m, 3H), 7.70 (d, 2H, J=8.2 Hz),8.17 (d, 2H, J=8.2 Hz).

Example 84-[4-Methoxyethoxymethoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid (a) Methyl4-[4-methoxyethoxymethoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 2(a), by reaction of 1.66 g (4.0mmol) of the methyl ester obtained in Example 1(d) with 571 μl (5.0mmol) of methoxyethoxymethyl chloride, 1.99 g (99%) of the expectedproduct are obtained in the form of a white crystalline solid.

¹H NMR (CDCl₃) δ 1.32 (s, 12H), 1.72 (s, 4H), 3.37 (d, 3H, J=0.5 Hz),3.52 (t, 2H, J=3.9 Hz), 3.77 (t, 2H, J=3.9 Hz), 3.93 (s, 3H), 5.26 (s,2H), 7.30 to 7.37 (m, 3H), 7.51 to 7.60 (m, 3H), 7.65 (d, 2H, J=8.2 Hz),8.09 (d, 2H, J=8.1 Hz).

(b)4-[4-Methoxyethoxymethoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 1.99 g (4.0mmol) of the methyl ester obtained in Example 8(a), 1.62 g (84%) of4-[4-methoxyethoxymethoxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid are obtained in the form of a white crystalline solid with amelting point of 218–219° C.

¹H NMR (CDCl₃) δ 1.32 (s, 12H), 1.72 (s, 4H), 3.37 (s, 3H), 3.52 (t, 2H,J=3.9 Hz), 3.76 (t, 2H, J=3.9 Hz), 5.26 (s, 2H), 7.30 to 7.37 (m, 3H),7.50 to 7.61 (m, 3H), 7.65 (d, 2H, J=8.3 Hz), 8.11 (d, 2H, J=8.3 Hz).

Example 9 4-[4-Benzyloxy-3-(5,6,7,8-tetrahydro-5, 5, 8,8-tetramethyl-2-naphthyl)phenyl]benzoic acid (a) Ethyl4-[4-benzyloxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 2(a), by reaction of 1.20 g (2.8mmol) of the ethyl ester obtained in Example 1(d) with 400 μl (3.2 mmol)of benzyl bromide, 1.23 g (85%) of the expected product are obtained inthe form of a colourless oil.

¹H NMR (CDCl₃) δ 1.23 (s, 6H), 1.32 (s, 6H), 1.41 (t, 3H, J=7.1 Hz),1.70 (s, 4H), 4.39 (q, 2H, J=7.1 Hz), 5.38 (s, 2H), 7.11 (d, 1H, J=8.5Hz), 7.28 to 7.36 (m, 6H), 7.53 (dd, 1H, J=8.5/2.4 Hz), 7.58 to 7.64 (m,2H), 7.65 (d, 2H, J=8.4 Hz), 8.09 (d, 2H, J=8.4 Hz).

(b)4-[4-Benzyloxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid

In a manner similar to that of Example 1(e), starting with 1.20 g (2.3mmol) of the ethyl ester obtained in Example 9(a), 970 mg (86%) of4-[4-benzyloxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoicacid are obtained in the form of a white crystalline solid with amelting point of 241–244° C.

¹H NMR (CDCl₃) δ 1.23 (s, 6H), 1.32 (s, 6H), 1.70 (s, 4H), 5.13 (s, 2H),7.12 (d, 1H, J=8.6 Hz), 7.28 to 7.36 (m, 6H), 7.54 (dd, 1H, J=8.5/2.4Hz), 7.58 (s, 1H), 7.64 (s, 1H), 7.66 (d, 2H, J=8.4 Hz), 8.11 (d, 2H,J=8.4 Hz).

Example 104′-(2,3-Dihydroxypropoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (racemic) (a) 2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl4-toluene-sulphonate (racemic)

5.29 g (40.0 mmol) of (2,2-dimethyl-[1,3]dioxolan-4-yl)methanol(Solketal®) and 10 ml of pyridine are introduced into a round-bottomedflask under an argon atmosphere. The mixture is cooled to 0° C., 8.39 g(44.0 mmol) of para-toluenesulphonic acid are added and the mixture isstirred for sixteen hours at room temperature. The reaction medium ispoured into a 1N HCl/ethyl ether mixture, extracted with ethyl ether,washed with water, dried over magnesium sulphate and evaporated. Theresidue obtained is purified by chromatography on a column of silicaeluted with dichloromethane. After evaporation of the solvents, 9.70 g(85%) of the expected product are collected in the form of yellowcrystals with a melting point of 45–47° C.

¹H NMR (CDCl₃) δ 1.31 (s, 3H), 1.34 (s, 3H), 2.45 (s, 3H), 3.74 to 3.80(m, 1H), 3.93 to 4.07 (m, 3H), 4.23 to 4.32 (m, 1H), 7.35 (d, 2H, J=8.1Hz), 7.80 (d, 2H, J=8.2 Hz).

(b) Ethyl4′-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate(racemic)

3.00 g (7.0 mmol) of the ethyl ester obtained in Example 1(d), 2.41 g(8.4 mmol) of the tosylate obtained in Example 10(a), 1.10 g (7.7 mmol)of potassium carbonate and 35 ml of DMF are introduced into around-bottomed flask under an argon atmosphere. The reaction medium isheated for one hour at 100° C., cooled, poured into a water/ethyl ethermixture, extracted with ethyl ether, washed with water, dried overmagnesium sulphate and evaporated. The residue obtained is purified bychromatography on a column of silica eluted with a mixture composed of50% dichloromethane and 50% heptane. After evaporation of the solvents,2.66 g (70%) of the expected product are collected in the form of acolourless oil.

¹H NMR (CDCl₃) δ 1.32 (s, 6H), 1.33 (s, 6H), 1.36 (s, 6H), 1.41 (t, 3H,J=7.1 Hz), 1.72 (s, 4H), 3.83 (dd, 1H, J=8.4/6.0 Hz), 3.94 to 4.07 (m,2H), 4.14 (dd, 1H, J=9.5/4.9 Hz), 4.39 (q, 2H, J=7.1 Hz), 4.40 (q, 1H,J=5.1 Hz), 7.06 (d, 1H, J=8.5 Hz), 7.28 (dd, 1H, J=8.1/1.8 Hz), 7.36 (d,1H, J=8.2 Hz), 7.53 (d, 1H, J=1.8 Hz), 7.55 (dd, 1H, J=8.5/2.3 Hz), 7.61(d, 1H, J=2.4 Hz), 7.65 (d, 2H, J=8.4 Hz), 8.09 (d, 2H, J=8.4 Hz).

(c) Ethyl4′-(2,3-dihydroxypropoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate(racemic)

1.66 g (3.2 mmol) of the ester obtained in Example 10(b), 6.12 g (32.2mmol) of para-toluene-sulphonic acid, 60 ml of dichloromethane and 5 mlof THF are introduced into a round-bottomed flask under an argonatmosphere. The reaction medium is stirred for sixteen hours at roomtemperature, poured into a water/ethyl ether mixture, extracted withethyl ether, washed with water, dried over magnesium sulphate andevaporated. The residue obtained is purified by chromatography on a cakeof silica eluted with a mixture composed of 40% ethyl acetate and 60%heptane. After evaporation of the solvents, 1.16 g (72%) of the expectedproduct are collected in the form of a white powder with a melting pointof 56° C.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.41 (t, 3H, J=7.1 Hz), 1.73 (s, 4H),1.87 (t, 1H, J—6.3 Hz), 2.49 (d, 1H, J=4.3 Hz), 3.60 to 3.80 (m, 2H);4.03 to 4.16 (m, 3H), 4.40 (q, 2H, J=7.1 Hz), 7.07 (d, 1H, J=8.4 Hz),7.29 (d, 1H, J=1.8 Hz), 7.38 (d, 1H, J=8.1 Hz), 7.48 (d, 1H, J=1.8 Hz),7.54 to 7.60 (m, 2H), 7.65 (d, 2H, J=8.4 Hz), 8.10 (d, 2H, J=8.5 Hz).

(d)4′-(2,3-Dihydroxypropoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (racemic)

In a manner similar to Example 1(e), starting with 1.16 g (2.3 mmol) ofthe ethyl ester obtained in Example 10(c), 897 mg (82%) of4′-(2,3-dihydroxypropoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 258° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 1.12 (s, 12H), 1.52 (s, 4H), 3.38 to3.53 (m, 2H), 3.79 to 3.94 (m, 3H), 6.91 (d, 1H, J=8.4 Hz), 7.10 to 7.17(m, 2H), 7.34 to 7.39 (m, 3H), 7.45 (d, 2H, J=8.4 Hz), 7.88 (d, 2H,J=8.4 Hz).

Example 114′-(2,2-Dimethyl)-[1,3]dioxolan-4-ylmethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-biphenyl-4-carboxylicacid (racemic)

In a manner similar to that of Example 1(e), starting with 1.00 g (1.8mmol) of the ester obtained in Example 10(b), 805 mg (85%) of4′-(2,2-dimethyl)-[1,3]dioxolan-4-ylmethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 206° C.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.36 (s, 6H), 1.73 (s, 4H), 3.84 (dd,1H, J=8.4/6.0 Hz), 3.96 to 4.09 (m, 2H), 4.15 (dd, 1H, J=9.5/4.9 Hz),4.42 (q, 1H, J=5.1 Hz), 7.08 (d, 1H, J=8.6 Hz), 7.29 (dd, 1H, J=8.1/1.7Hz), 7.36 (d, 1H, J=8.2 Hz), 7.54 (d, 1H, J=1.6 Hz), 7.57 (dd, 1H,J=8.5/2.3 Hz), 7.63 (d, 1H, J=2.3 Hz), 7.69 (d, 2H, J=8.4 Hz), 8.17 (d,2H, J=8.4 Hz).

Example 124′-(2-Morpholin-4-ylethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Ethyl4′-(2-morpholin-4-ylethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 2(a), by reaction of 1.08 g (2.5mmol) of the ethyl ester obtained in Example 1(d) with 1.39 g (7.5 mmol)of 4-(2-chloroethyl)morpholine hydrochloride, 500 mg (37%) of theexpected product are obtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.32 (s, 12H), 1.41 (t, 3H, J=7.1 Hz), 1.72 (s, 4H),2.45 (t, 2H, J=4.6 Hz), 2.77 (t, 2H, J=5.8 Hz), 3.64 (t, 2H, J=4.7 Hz),4.16 (t, 2H, J=5.8 Hz), 4.40 (q, 2H, J=7.2 Hz), 7.05 (d, 1H, J=8.5 Hz),7.34 (s, 2H), 7.52 (s, 1H), 7.56 (dd, 1H, J=8.4/2.4 Hz), 7.61 (d, 1H,J=2.3 Hz), 7.65 (d, 2H, J=8.4 Hz), 8.09 (d, 2H, J=8.4 Hz).

(b)4′-(2-Morpholin-4-ylethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 500 mg (0.92mmol) of the ethyl ester obtained in Example 12(a), 320 mg (70%) of4′-(2-morpholin-4-ylethoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 270–272° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 1.31 (s, 12H), 1.73 (s, 4H), 2.58 to2.61 (m, 2H), 3.23 (d, 2H, J=11.9 Hz), 3.38 (br s, 2H), 3.67 (d, 2H,J=12.6 Hz), 4.02 (t, 2H, J=11.9 Hz), 4.61 (br s, 2H), 7.08 (d, 1H, J=8.3Hz), 7.22 (dd, 1H, J=8.1/1.6 Hz), 7.35 (d, 1H, J=8.1 Hz), 7.47 (s, 1H),7.55 (s, 1H), 7.61 (dd, 1H, J=8.1/2.4 Hz), 7.64 (d, 2H, J=8.4 Hz), 8.09(d, 2H, J=8.3 Hz).

Example 13 Methyl2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate(a) Methyl3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-4′-trifluoromethanesulphonyloxybiphenyl-4-carboxylate

1.66 g (4.0 mmol) of the methyl ester obtained in Example 1(d), 1.56 g(12.8 mmol) of 4-dimethylaminopyridine and 40 ml of dichloromethane areintroduced into a three-necked flask under a stream of nitrogen. Themixture is cooled to 0° C., 701 μl (4.2 mmol) oftrifluoromethanesulphonic anhydride are added dropwise and this mixtureis stirred at room temperature for one hour. The reaction medium ispoured into a mixture of hydrochloric acid (1N) and dichloromethane, andthe organic phase is separated out after settling has taken place, driedover magnesium sulphate and evaporated. The residue obtained is purifiedby chromatography on a column of silica eluted with a mixture ofdichloromethane and hexane (40/60). 1.90 g (87%) of the expected productare collected in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.32 (s, 6H), 1.73 (s, 4H), 3.95 (s, 3H),7.23 (dd, 1H, J=8.2/1.8 Hz), 7.39 to 7.48 (m, 3H), 7.60 to 7.70 (m, 2H),7.72 (d, 2H, J=8.5 Hz), 8.13 (d, 2H, J=8.3 Hz).

(b) Methyl2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

469 mg (3.8 mmol) of phenylboronic acid, 1.91 g (3.5 mmol) of methyl4-[4-trifluoromethanesulphonate-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-phenyl]benzoate,4.54 ml (9.1 mmol) of sodium carbonate solution (2M), 296 mg of lithiumchloride and 30 ml of DMF are introduced into a three-necked flask. Thereaction medium is degassed by bubbling nitrogen through, 129 mg (0.11mmol) of tetrakistriphenylphosphinepalladium(0) are added and thismixture is heated at 90° C. for twenty hours. The reaction medium isevaporated to dryness and the residue is taken up in water and ethylether and acidified. The organic phase is separated out after settlinghas taken place, dried over magnesium sulphate and evaporated. Theresidue obtained is purified by chromatography on a column of silicaeluted with a mixture of ethyl ether and heptane (5/95). 480 mg (30%) ofthe expected product are collected in the form of a yellow oil.

¹H NMR (CDCl₃) δ 0.90 (s, 6H), 1.26 (s, 6H), 1.55 to 1.63 (m, 4H), 3.90(s, 3H), 6.90 (d, 1H, J=1.7 Hz), 7.14 to 7.28 (m, 7H), 7.49 (d, 1H,J=8.0 Hz), 7.62 (dd, 1H, J=8.0/1.9 Hz), 7.70 to 7.73 (m, 1H), 7.71 (d,2H, J=8.4 Hz), 8.11 (d, 2H, J=8.4 Hz).

Example 142′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 950 mg (2.0mmol) of the methyl ester obtained in Example 13(b), 820 mg (89%) of2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are collected in the form of a white powder with a melting point of287–288° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.56 to 1.64 (m, 4H), 6.89(d, 1H, J=1.8 Hz), 7.14 to 7.33 (m, 7H), 7.52 (d, 1H, J=7.9 Hz), 7.67(dd, 1H, J=8.0/1.9 Hz), 7.72 to 7.73 (m, 1H), 7.75 (d, 2H, J=8.6 Hz),8.15 (d, 2H, J=8.4 Hz).

Example 154-(Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetraydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) 4-Methoxymethoxybromobenzene

In a manner similar to that of Example 7(a), by reaction of 48.84 g(282.3 mmol) of 4-bromophenol with 25.0 ml (310.5 mmol) of chloromethylmethyl ether, 63.85 g (100%) of the expected product are obtained in theform of a beige-coloured oil.

¹H NMR (CDCl₃) δ 3.46 (s, 3H), 5.14 (s, 2H), 6.92 (d, 2H, J=9.0 Hz),7.38 (d, 2H, J=9.0 Hz).

(b) 4-Methoxymethoxyphenylboronic acid

In a manner similar to that of Example 1(a), starting with 63.81 g(293.0 mmol) of 4-methoxymethoxybromobenzene, 35.42 g (80%) of theexpected product are obtained in the form of a white solid with amelting point of 122° C.

¹H NMR (CDCl₃) δ 3.52 (s, 3H), 5.27 (s, 2H), 7.15 (d, 2H, J=8.6 Hz),8.16 (d, 2H, J=8.6 Hz).

(c) Ethyl4-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13 (b), by reaction of 357 mg(2.0 mmol) of the compound obtained in Example 15(b) with 1.00 g (1.8mmol) of the analogue (ethyl ester) of the compound obtained in Example13(a), 880 mg (13%) of the expected product are obtained in the form ofa colourless oil.

¹H NMR (CDCl₃) δ 0.94 (s, 6H), 1.28 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.58 to 1.63 (m, 4H), 3.46 (s, 3H), 4.41 (q, 2H, J=7.1 Hz), 5.14 (s,2H), 6.90 (d, 1H, J=1.8 Hz), 6.91 (d, 2H, J=8.7 Hz), 7.08 (d, 2H, J=8.7Hz), 7.17 (dd, 1H, J=8.1/1.9 Hz), 7.29 (d, 1H, J=8.1 Hz), 7.50 (d, 1H,J=7.9 Hz), 7.64 (dd, 1H, J=8.0/2.0 Hz), 7.72 (d, 1H, J=1.9 Hz), 7.74 (d,2H, J=8.4 Hz), 8.13 (d, 2H, J=8.4 Hz).

(d)4-Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 870 mg (1.6mmol) of the ethyl ester obtained in Example 15(c), 750 mg (91%) of4-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are collected in the form of a white powder with a melting point of249–251° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 0.94 (s, 6H), 1.28 (s, 6H), 1.54 to1.66 (m, 4H), 3.45 (s, 3H), 5.14 (s, 2H), 6.89 (d, 1H, J=1.9 Hz), 6.91(d, 2H, J=8.6 Hz), 7.08 (d, 2H, J=8.6 Hz), 7.17 (dd, 1H, J=8.1/1.7 Hz),7.31 (d, 1H, J=8.1 Hz), 7.28 (d, 1H, J=8.1 Hz), 7.50 (d, 1H, J=7.9 Hz),7.65 (dd, H, J=8.0/1.8 Hz), 7.71 (d, 1H, J=1.9 Hz), 7.74 (d, 2H, J=8.3Hz), 8.14 (d, 2H, J=8.3 Hz).

Example 16 4-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic acid(a) Ethyl4-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

3.81 g (5.5 mmol) of the compound obtained in Example 15(c), 100 ml ofethanol and 50 ml of THF are introduced into a 250 ml three-necked flaskunder a stream of nitrogen. 3.5 ml of concentrated sulphuric acid areadded dropwise. The reaction medium is heated for fifteen minutes at 60°C., water is then added, the mixture is extracted with ethyl ether andthe organic phase is washed with water to neutral pH, dried overmagnesium sulphate and filtered, and the solvents are evaporated off.The residue obtained is purified by chromatography on a column of silicaeluted with heptane and then with a mixture composed of 20% ethylacetate and 80% heptane. After evaporation of the solvents, 2.60 g (74%)of the expected compound are collected in the form of a white powderwith a melting point of 177–179° C.

¹H NMR (CDCl₃) δ 0.98 (s, 6H), 1.27 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.58 to 1.65 (m, 4H), 4.41 (q, 2H, J=7.1 Hz), 4.91 (s, 1H), 6.71 (d, 2H,J=8.6 Hz), 6.94 (d, 1H, J=1.8 Hz), 7.03 (d, 2H, J=8.6 Hz), 7.13 (dd, 1H,J=8.1/1.9 Hz), 7.27 (d, 2H, J=7.4 Hz), 7.49 (d, 1H, J=8.0 Hz), 7.64 (dd,1H, J=8.0/1.9 Hz), 7.71 (d, 1H, J=1.9 Hz), 7.73 (d, 2H, J=8.5 Hz), 8.13(d, 2H, J=8.4 Hz).

(b)4-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 980 mg (1.9mmol) of the ethyl ester obtained in Example 16(a), 790 mg (80%) of4-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-41-carboxylicacid are collected in the form of a white powder with a melting point of262–266° C.

¹H NMR (CDCl₃) δ 0.99 (s, 6H), 1.27-(s, 6H), 1.55 to 1.67 (m, 4H), 6.72(d, 2H, J=8.5 Hz), 6.97 (d, 1H, J=1.7 Hz), 6.98 (d, 2H, J=8.5 Hz), 7.12(dd, 1H, J=8.0/1.6 Hz), 7.25 (d, 1H, J=8.1 Hz), 7.49 (d, 1H, J=7.9 Hz),7.64 (dd, 1H, J=8.0/1.6 Hz), 7.69 (d, 1H, J=1.7 Hz), 7.73 (d, 2H, J=8.3Hz), 8.13 (d, 2H, J=8.3 Hz).

Example 174-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl4-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 7(a), by reaction of 1.40 g (2.8mmol) of the compound obtained in Example 16(a) with 250 μl (4.2 mmol)of methyl iodide, 1.35 g (96%) of the expected product are obtained inthe form of a yellow solid with a melting point of 112–115° C.

¹H NMR (CDCl₃) δ 1.27 (s, 12H), 1.42 (t, 3H, J=7.1 Hz), 1.58 to 1.65 (m,4H), 3.78 (s, 3H); 4.41 (q, 2H, J=7.1 Hz), 6.78 (d, 2H, J=8.7 Hz), 6.93(d, 1H, J=1.9 Hz), 7.08 (d, 2H, J=8.7 Hz), 7.14 (dd, 1H, J=8.1/1.9 Hz),7.27 (d, 1H, J=7.0 Hz), 7.50 (d, 1H, J=7.9 Hz), 7.64 (dd, 1H, J=8.0/4.0Hz), 7.71 (d, 1H, J=1.9 Hz), 7.74 (d, 2H, J=8.5 Hz), 8.12 (d, 2H, J=8.4Hz).

(b)4-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.30 g (2.7mmol) of the ethyl ester obtained in Example 17(a), 960 mg (74%) of4-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-41-carboxylicacid are collected in the form of a white powder with a melting point of262–266° C.

¹H NMR (CDCl₃) δ 0.96 (s, 6H), 1.27 (s, 6H), 1.55 to 1.67 (m, 4H), 3.78(s, 3H), 6.78 (d, 2H, J=8.7 Hz), 6.93 (d, 1H, J=1.6 Hz), 7.08 (d, 2H,J=8.6 Hz), 7.14 (dd, 1H, J=8.2/1.7 Hz), 7.27 (d, 1H, J=8.1 Hz), 7.50 (d,1H, J=8.0 Hz), 7.65 (dd, 1H, J=8.0/1.8 Hz), 7.72 (d, 1H, J=1.6 Hz), 7.75(d, 2H, J=8.4 Hz), 8.17 (d, 2H, J=8.3 Hz).

Example 183-Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) 3-Methoxymethoxybromobenzene

In a manner similar to that of Example 7(a), by reaction of 100.00 g(577.9 mmol) of 3-bromophenol with 48.28 g (635.8 mmol) of chloromethylmethyl ether, 135.32 g (100%) of the expected product are obtained inthe form of a pale beige oil.

¹H NMR (CDCl₃) δ 3.46 (s, 3H), 5.15 (s, 2H), 6.92 to 7.00 (m, 1H), 7.10to 7.14 (m, 2H), 7.18 to 7.22 (m, 1H).

(b) 3-Methoxymethoxyphenylboronic acid

In a manner similar to that of Example 1(a), starting with 125.00 g(575.8 mmol) of 3-methoxymethoxybromobenzene, 86.00 g (100%) of theexpected product are obtained in the form of a yellow oil which will beused directly for the following step.

(c) Ethyl3-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13 (b), by reaction of 3.50 g(19.3 mmol) of the compound obtained in Example 18(b) with 9.00 g (16.1mmol) of the analogue (ethyl ester) of the compound obtained in Example13(a), 7.70 g (87%) of the expected product are obtained in the form ofa white solid with a melting point of 103–104° C.

¹H NMR (CDCl₃) δ 0.96 (s, 6H), 1.27 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.58 to 1.65 (m, 4H), 3.36 (s, 3H), 4.41 (q, 2H, J=7.1 Hz), 4.89 (s,2H), 6.76 (t, 1H, J=2.1 Hz), 6.85 (dd, 1H, J=8.2/2.4 Hz), 6.91 (m, 1H)6.93 (d, 1H, J=1.6 Hz), 7.13 to 7.30 (m, 3H), 7.54 (d, 1H, J=7.9 Hz),7.65 (dd, 1H, J=8.0/1.9 Hz), 7.72 (s, 1H), 7.74 (d, 2H, J=8.4 Hz), 8.13(d, 2H, J=8.4 Hz).

(d)3-Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.20 g (2.2mmol) of the ethyl ester obtained in Example 18(c), 1.03 g (90%) of3-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are collected in the form of a white powder with a melting point of212° C.

¹H NMR (CDCl₃) δ 0.96 (s, 6H), 1.27 (s, 6H), 1.56 to 1.66 (m, 4H), 3.37(s, 3H), 4.90 (s, 2H), 6.77 (d, 1H, J=1.9 Hz), 6.85 (dd, 1H, J=8.2/1.9Hz), 6.91 to 6.94 (m, 2H), 7.16 (dd, 1H, J=8.1/1.8 Hz), 7.17 to 7.23 (m,1H), 7.29 (d, 1H, J=8.1 Hz), 7.55 (d, 1H, J=8.0 Hz), 7.68 (dd, 1H,J=8.0/1.9 Hz), 7.74 (d, 1H, J=1.8 Hz), 7.78 (d, 2H, J=8.4 Hz), 8.21 (d,2H, J=8.4 Hz).

Example 193-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl3-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4-carboxylate

In a manner similar to that of Example 16(a), starting with 6.26 g (11.4mmol) of the compound obtained in Example 18(c), 5.63 g (98%) of theexpected product are obtained in the form of a white solid with amelting point of less than 70° C.

¹H NMR (CDCl₃) δ 0.95 (s, 6H), 1.27 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.58 to 1.65 (m, 4H), 4.41 (q, 2H, J=7.1 Hz), 4.95 (s, 1H), 6.63 to 6.76(m, 3H), 6.94 (d, 1H, J=1.8 Hz), 7.11 (t, 1H, J=7.9 Hz), 7.15 (dd, 1H,J=8.2/1.9 Hz), 7.28 (d, 1H, J=8.1 Hz), 7.49 (d, 1H, J=7.9 Hz), 7.63 (dd,1H, J=8.2/1.9 Hz), 7.71 to 7.73 (m, 1H), 7.73 (d, 2H, J=8.4 Hz), 8.13(d, 2H, J=8.4 Hz).

(b)3-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.05 g (2.1mmol) of the ethyl ester obtained in Example 19(a), 820 mg (83%) of3-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-40-carboxylicacid are collected in the form of a white powder with a melting point of260–263° C.

¹H NMR (CDCl₃) δ 0.96 (s, 6H), 1.27 (s, 6H), 1.57 to 1.64 (m, 4H), 6.58(d, 1H, J=7.7 Hz), 6.69 (dd, 1H, J=8.0/2.0 Hz), 6.75 (d, 1H, J=2.0 Hz),6.98 (d, 1H, J=1.7 Hz), 7.03 (t, 1H, J=7.8 Hz), 7.16 (dd, 1H, J=7.9/1.8Hz), 7.26 (d, 1H, J=8.1 Hz), 7.49 (d, 1H, J=7.9 Hz), 7.63 (dd, 1H,J=8.0/1.9 Hz), 7.71 (d, 1H, J=1.9 Hz), 7.73 (d, 2H, J=8.4 Hz), 8.14 (d,2H, J=8.4 Hz).

Example 203-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl3-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 7(a), by reaction of 1.20 g (2.4mmol) of the compound obtained in Example 19(a) with 190 μl (3.1 mmol)of methyl iodide, 1.08 g (87%) of the expected product are obtained inthe form of a white solid with a melting point of 116–118° C.

¹H NMR (CDCl₃) δ 0.96 (s, 6H), 1.27 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.58 to 1.66 (m, 4H), 3.49 (s, 3H), 4.41 (q, 2H, J=7.1 Hz), 6.53 (d, 1H,J=1.3 Hz), 6.74 (dd, 1H, J=7.6/2.5 Hz), 6.89 (d, 1H, J=7.6 Hz), 6.95 (d,1H, J=1.6 Hz), 7.12 to 7.30 (m, 3H), 7.56 (d, 1H, J=8.0 Hz), 7.67 (dd,1H, J=8.0/1.8 Hz), 7.72 to 7.74 (m, 1H), 7.74 (d, 2H, J=8.3 Hz), 8.13(d, 2H, J=8.3 Hz).

(b)3-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.07 g (2.1mmol) of the ethyl ester obtained in Example 20(a), 930 mg (92%) of3-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are collected in the form of a white powder with a melting point of258–259° C.

¹H NMR (CDCl₃) δ 0.96 (s, 6H), 1.27 (s, 6H), 1.58 to 1.65 (m, 4H), 3.49(s, 3H), 6.54 (d, 1H, J=1.6 Hz), 6.72 (dd, 1H, J=7.6/2.1 Hz), 6.89 (d,1H, J=7.6 Hz), 6.94 (d, 1H, J=1.7 Hz), 7.14 (d, 1H, J=7.8 Hz), 7.21 (d,1H, J=7.9 Hz), 7.28 (d, 1H, J=8.1 Hz), 7.56 (d, 1H, J=8.0 Hz), 7.68 (dd,1H, J=8.0/1.9 Hz), 7.68 to 7.70 (m, 1H), 7.74 (d, 2H, J=8.3 Hz), 8.14(d, 2H, J=8.3 Hz).

Example 212-Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) 2-Methoxymethoxybromobenzene

In a manner similar to that of Example 7(a), by reaction of 15.00 g(86.7 mmol) of 2-bromophenol with 8.40 g (104.0 mmol) of chloromethylmethyl ether, 18.80 g (100%) of the expected product are obtained in theform of a beige-coloured oil.

¹H NMR (CDCl₃) δ 3.53 (s, 3H), 5.25 (s, 2H), 6.89 (dt, 1H, J=7.5/1.6Hz), 7.15 (dd, 1H, J=8.311.6 Hz), 7.25 (dt, 1H, J=7.3/1.6 Hz), 7.54 (dd,1H, J=7.9/1.6 Hz).

(b) 2-Methoxymethoxyphenylboronic acid

In a manner similar to that of Example 1(a), starting with 19.00 g (8.7mmol) of 2-methoxymethoxybromobenzene, 11.00 g (70%) of the expectedproduct are obtained in the form of a white solid with a melting pointof 63–66° C.

¹H NMR (CDCl₃) δ 3.51 (s, 3H), 5.31 (s, 2H), 6.21 (s, 2H), 7.07 (d, 1H,J=7.3 Hz), 7.14 (d, 1H, J=8.8 Hz), 7.43 (dt, 1H, J=8.6/1.9 Hz), 7.87(dd, 1H, J=7.3/1.8 Hz).

(c) Ethyl2-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(b), by reaction of 2.73 g(15.0 mmol) of the compound obtained in Example 21(b) with 7.00 g (12.5mmol) of the analogue (ethyl ester) of the compound obtained in Example13(a), 1.50 g (22%) of the expected product are obtained in the form ofa white solid with a melting point of 132–135° C.

¹H NMR (CDCl₃) δ 0.91 (br s, 6H), 1.24 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.54 to 1.63 (m, 4H), 3.10 (s, 3H), 4.41 (q, 2H, J=7.1 Hz), 4.40 to 4.80(br s, 2H), 6.96 (d, 1H, J=1.8 Hz), 7.02 to 7.29 (m, 7H), 7.47 (d, 1H,J=8.7 Hz), 7.65 (dd, 1H, J=7.9/1.9 Hz), 7.74 (s, 1H), 7.76 (d, 2H, J=8.4Hz), 8.13 (d, 2H, J=8.4 Hz).

(d)2-Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 470 mg (0.86mmol) of the ethyl ester obtained in Example 21(c), 360 mg (81%) of2-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are collected in the form of a white powder with a melting point of218–221° C.

¹H NMR (CDCl₃) δ 0.91 (br s, 6H), 1.24 (s, 6H), 1.52 to 1.64 (m, 4H),3.10 (s, 3H), 4.40 to 4.80 (br s, 2H), 6.97 (d, 1H, J=1.8 Hz), 7.02 to7.28 (m, 6H), 7.47 (d, 1H, J=7.9 Hz), 7.67 (dd, 1H, J=7.9/1.9 Hz), 7.75(d, 1H, J=1.8 Hz), 7.80 (d, 2H, J=8.4 Hz), 8.21 (d, 2H, J=8.3 Hz).

Example 222-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl2-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 16(a), starting with 1.10 g (2.0mmol) of the compound obtained in Example 21(c), 1.00 g (99%) of theexpected product are obtained in the form of a white solid with amelting point of 161–163° C.

¹H NMR (CDCl₃) δ 0.93 (s, 6H), 1.25 (s, 6H), 1.43 (t, 3H, J=7.2 Hz),1.55 to 1.65 (m, 4H), 4.41 (q, 2H, J=7.1 Hz), 6.81 (d, 1H, J=8.1 Hz),6.90 (t; 1H, J=7.5 Hz), 6.99 (d, 1H, J=1.9 Hz), 7.10 to 7.20 (m, 3H),7.28 (d, 1H, J=8.7 Hz), 7.50 (d, 1H, J=7.9 Hz), 7.69 (dd, 1H, J=7.9/1.9Hz), 7.75 (d, 2H, J=8.5 Hz), 7.78 (d, 1H, J=1.9 Hz), 8.15 (d, 2H, J=8.4Hz).

(b)2-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 390 mg (0.77mmol) of the ethyl ester obtained in Example 22(a), 315 mg (86%) of2-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are collected in the form of a white powder with a melting point of265–269° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 0.93 (s, 6H), 1.25 (s, 6H), 1.55 to1.62 (m, 4H), 6.77 to 6.85 (m, 2H), 7.02 to 7.13 (m, 3H), 7.18 to 7.27(m, 2H), 7.51 (d, 1H, J=7.9 Hz), 7.66 (dd, 1H, J=7.9/1.9 Hz), 7.73 (d,1H, J=7.9 Hz), 7.74 (d, 2H, J=8.3 Hz), 8.14 (d, 2H, J=8.3 Hz).

Example 232-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl2-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 7(a), by reaction of 580 mg (1.2mmol) of the compound obtained in Example 22(a) with 110 μl (1.5 mmol)of methyl iodide, 530 mg (89%) of the expected product are obtained inthe form of a white solid with a melting point of 133–136° C.

¹H NMR (CDCl₃) δ 0.93 (br s, 6H), 1.24 (s, 6H), 1.42 (t, 3H J=7.1 Hz),1.56 to 1.63 (m, 4H), 3.27 (s, 3H), 4.40 (q, 2H, J=7.1 Hz), 6.71 (d, 1H,J=8.0 Hz), 6.94 (d, 1H, J=1.8 Hz), 6.98 (d, 1H, J=7.3 Hz), 7.12 (dd, 1H,J=8.1/1.9 Hz), 7.19 to 7.26 (m, 3H), 7.47 (d, 1H, J=7.9 Hz), 7.64 (dd,1H, J=7.9/1.9 Hz), 7.71 (d, 1H, J=1.9 Hz), 7.75 (d, 2H, J=8.6 Hz), 8.12(d, 2H, J=8.4 Hz).

(b)2-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 530 mg (1.0mmol) of the ethyl ester obtained in Example 23(a), 435 mg (87%) of2-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are collected in the form of a white powder with a melting point of239–243° C.

¹H NMR (CDCl₃) δ 0.93 (s, 6H), 1.25 (s, 6H), 1.54 to 1.63 (m, 4H), 3.28(s, 3H), 6.71 (d, 1H, J=8.1 Hz), 6.95 to 7.01 (m, 2H), 7.14 (d, 1H,J=8.1 Hz), 7.20 to 7.25 (m, 3H), 7.49 (d, 1H, J=7.9 Hz), 7.67 (d, 1H,J=7.9 Hz), 7.74 (d, 1H, J=1.8 Hz), 7.79 (d, 2H, J=8.2 Hz), 8.21 (d, 2H,J=8.2 Hz).

Example 242′-Methoxymethoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) 4-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)phenol.

In a manner similar to that of Example 1(d), by reaction of 53.00 g(230.3 mmol) of the boronic acid obtained in Example 1(a) with 23.10 g(133.6 mmol) of 4-bromophenol, 60.00 g (70%) of the expected compoundare obtained in the form of a white solid with a melting point of137–140° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.71 (s, 4H), 4.77 (s, 1H),6.89 (d, 2H, J=8.6 Hz), 7.30 (dd, 1H, J=8.2/1.9 Hz), 7.36 (d, 1H, J=8.1Hz), 7.45 (d, 1H, J=1.9 Hz), 7.46 (d, 2H, J=8.6 Hz).

(b) 2-Bromo-4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-phenol

39.00 g (139.0 mmol) of the compound obtained in Example 24(a) and 350ml of dichloromethane are introduced into a round-bottomed flask. 23.40g (146.0 mmol) of bromine dissolved in 50 ml of dichloromethane areadded dropwise and the mixture is stirred for thirty minutes at roomtemperature. The reaction medium is evaporated to dryness, the residueis taken up in water and ethyl acetate and the organic phase isseparated out after settling has taken place, washed with aqueous sodiummetabisulphite solution, dried over magnesium sulphate, filtered andevaporated. 40.60 g (80%) of the expected product are collected in theform of a yellow oil.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.34 (s, 6H), 1.71 (s, 4H), 5.49 (s, 1H),7.07 (d, 1H, J=8.4 Hz), 7.27 (dd, 1H, J=7.7/2.0 Hz), 7.36 (d, 1H, J=8.2Hz), 7.43 (dd, 1H, J=7.8/2.0 Hz), 7.51 (d, 1H, J=2.1 Hz), 7.65 (d, 1H,J=2.1 Hz)

(c)6-(3-Bromo-4-methoxymethoxyphenyl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene

In a manner similar to that of Example 7(a), by reaction of 40.60 g(113.1 mmol) of the compound obtained in Example 24(b) with 10.65 ml(135.0 mmol) of chloromethyl methyl ether, 45.00 g (98%) of the expectedproduct are obtained in the form of a brown oil.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.71 (s, 4H), 3.55 (s, 3H),5.28 (s, 2H), 7.20 (d, 1H, J=8.5 Hz), 7.27 (dd, 1H, J=8.2/1.9 Hz), 7.36(d, 1H, J=8.2 Hz), 7.43 (dd, 1H, J=7.8/2.0 Hz), 7.51 (d, 1H, J=2.1 Hz),7.75 (d, 1H, J=2.2 Hz).

(d)2-Methoxymethoxy-5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylboronicacid

In a manner similar to that of Example 1(a), starting with 45.00 g(112.0 mmol) of the compound obtained in Example 24(c), 41.50 g (100%)of the expected product are obtained in the form of a brown oil which isused directly for the following step.

(e) Ethyl2′-methoxymethoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 1(d), by reaction of 41.20 g(112.0 mmol) of the compound obtained in Example 24(d) with 30.90 g(112.0 mmol) of ethyl 4-iodobenzoate, 18.00 g (34%) of the expectedproduct are obtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.41 (t, 3H, J=7.1 Hz),1.72 (s, 4H), 3.40 (s, 3H), 4.40 (q, 2H, J=7.1 Hz), 5.15 (s, 2H), 7.23to 7.39 (m, 3H), 7.44 to 7.59 (m, 3H), 7.65 (d, 2H, J=8.1 Hz), 8.12 (d,2H, J=8.2 Hz).

(f)2′-Methoxymethoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.00 g (2.1mmol) of the ester obtained in Example 24(e), 660 mg (70%) of2′-methoxymethoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of beige-coloured crystals with a meltingpoint of 183–185° C.

¹H NMR (CDCl₃) δ 1.32 (s, 6H), 1.34 (s, 6H), 1.72 (s, 4H), 3.42 (s, 3H),5.18 (s, 2H), 7.28 to 7.40 (m, 3H), 7.49 to 7.56 (m, 3H), 7.70 (d, 2H,J=8.2 Hz), 8.19 (d, 2H, J=8.2 Hz).

Example 252′-Methoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Ethyl2′-hydroxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 16(a), starting with 17.00 g(36.0 mmol) of the compound obtained in Example 24(e), 15.10 g (98%) ofthe expected product are obtained in the form of a beige-coloured solidwith a melting point of 148–152° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.72 (s, 4H), 4.41 (q, 2H, J=7.2 Hz), 5.29 (br s, 1H), 7.04 (d, 1H,J=8.1 Hz), 7.31 to 7.39 (m, 2H), 7.46 to 7.52 (m, 3H), 7.63 (d, 2H,J=8.3 Hz), 8.17 (d, 2H, J=8.3 Hz).

(b) Ethyl2′-methoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 7(a), by reaction of 1.53 g (3.6mmol) of the compound obtained in Example 25(a) with 330 μl (5.4 mmol)of methyl iodide, 1.40 g (88%) of the expected product are obtained inthe form of a brown oil.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),3.86 (s, 3H), 1.72 (s, 4H), 4.41 (q, 2H, J=7.2 Hz), 7.04 (d, 1H, J=8.1Hz), 7.31 to 7.39 (m, 2H), 7.46 to 7.52 (m, 3H), 7.63 (d, 2H, J=8.3 Hz),8.17 (d, 2H, J=8.3 Hz).

(c)2′-Methoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.40 g (3.6mmol) of the ester obtained in Example 25(b), 1.07 g (72%) of2′-methoxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 233–235° C.

¹H NMR (CDCl₃) δ 1.32 (s, 6H), 1.34 (s, 6H), 1.72 (s, 4H), 3.86 (s, 3H),7.07 (d, 1H, J=8.4 Hz), 7.32 to 7.39 (m, 2H), 7.49 to 7.58 (m, 3H), 7.65(d, 2H, J=8.3 Hz), 8.11 (dd, 1H, J=8.3 Hz).

Example 262′-Propyloxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Ethyl2′-propyloxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 7(a), by reaction of 1.34 g (3.1mmol) of the compound obtained in Example 25(a) with 460 μl (4.7 mmol)of propyl iodide, 1.30 g (88%) of the expected product are obtained inthe form of a colourless oil.

¹H NMR (CDCl₃) δ 0.98 (t, 3H, J=7.3 Hz), 1.32 (s, 6H), 1.33 (s, 6H),1.42 (t, 3H, J=7.1 Hz), 1.72 to 1.77 (m, 2H), 1.72 (s, 4H), 3.98 (t, 2H,J=6.4 Hz), 4.41 (q, 2H, J=7.1 Hz), 7.04 (d, 1H, J=9.1 Hz), 7.31 to 7.39(m, 2H), 7.49 to 7.54 (m, 3H), 7.67 (d, 2H, J=8.4 Hz), 8.09 (d, 2H,J=8.4 Hz).

(b)2′-Propyloxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.30 g (3.1mmol) of the ester obtained in Example 26(a), 850 mg (61%) of2′-propyloxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 199–204° C.

¹H NMR (CDCl₃) δ 0.98 (t, 3H, J=7.3 Hz), 1.71 to 1.81 (m, 2H), 1.72 (s,4H), 3.99 (t, 2H, J=6.4 Hz), 7.05 (d, 1H, J=9.2 Hz), 7.35 to 7.40 (m,2H), 7.49 to 7.56 (m, 3H), 7.72 (d, 2H, J=8.4 Hz), 8.17 (d, 2H, J=8.4Hz).

Example 272′-Hydroxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.00 g (2.3mmol) of the ester obtained in Example 25(a), 800 mg (86%) of2′-hydroxy-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 264–267° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.71 (s, 4H), 7.07 (d, 1H,J=8.3 Hz), 7.34 to 7.37 (m, 2H), 7.41 (dd, 1H, J=8.4/2.3 Hz), 7.47 to7.49 (m, 2H), 7.72 (d, 2H, J=8.3 Hz), 8.11 (d, 2H, J=8.4 Hz).

Example 284′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;2′,1″]terphenyl-4″-carboxylicacid (a) Ethyl5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-2′-trifluoromethanesulphonyloxybiphenyl-4-carboxylate

2.00 g (4.7 mmol) of the ethyl ester obtained in Example 25(a), 1.30 g(4.9 mmol) of 4-nitrophenyl triflate, 1.30 g (9.3 mmol) of potassiumcarbonate and 30 ml of N,N-dimethylformamide are introduced into athree-necked flask under a stream of nitrogen. The reaction medium isstirred at room temperature for sixteen hours, poured into a water/ethylether mixture, washed with water, dried over magnesium sulphate andevaporated. 2.60 g (100%) of the expected product are collected in theform of yellow crystals with a melting point of 110–113° C.

¹H NMR (CDCl₃) δ 1.32 (s, 6H), 1.34 (s, 6H), 1.43 (t, 3H, J=7.1 Hz),1.73 (s, 4H), 4.42 (t, 2H, J=7.2 Hz), 7.34 (dd, 1H, J=8.2/1.9 Hz), 7.39to 7.50 (m, 3H), 7.59 (d, 2H, J=8.4 Hz), 7.60 to 7.65 (m, 2H), 8.17 (d,2H, J=8.4 Hz).

(b) Ethyl4′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;2′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(b), by reaction of 2.60 g (4.6mmol) of the compound obtained in Example 28(a) with 626 mg (5.1 mmol)of phenylboronic acid, 1.10 g (47%) of the expected product are obtainedin the form of yellow crystals with a melting point of 233–235° C.

¹H NMR (CDCl₃) δ 1.21 (t, 3H, J=7.1 Hz), 1.32 (s, 6H), 1.35 (s, 6H),1.68 (s, 4H), 4.29 (q, 2H, J=7.0 Hz), 7.25 to 7.32 (m, 5H), 7.44 (d, 2H,J=8.2 Hz), 7.54 to 7.70 (m, 3H), 7.89 to 7.91 (m, 3H), 8.06 (d, 2H,J=8.2 Hz).

(c)4′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;2′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.00 g (2.0mmol) of the ester obtained in Example 28(b), 700 mg (77%) of4′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;2′,1″]terphenyl-4″-carboxylicacid are obtained in the form of beige-coloured crystals with a meltingpoint of 258–262° C.

¹H NMR (DMSO-d₆) δ 1.28 (s, 6H), 1.32 (s, 6H), 1.68 (s, 4H), 7.11 to7.15 (m, 2H), 7.25 to 7.28 (m, 3H), 7.32 (d, 2H, J=8.2 Hz), 7.43 (d, 1H,J=8.2 Hz), 7.46 (d, 1H, J=1.8 Hz), 7.51 (d, 1H, J=8.0 Hz), 7.62 to 7.64(m, 2H), 7.74 (dd, 1H, J=8.0/1.8 Hz), 7.81 (d, 2H, J=8.3 Hz).

Example 292′-Methoxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) 1,3-Dibromo-2-methoxymethoxybenzene

In a manner similar to that of Example 7(a), by reaction of 19.16 g(76.1 mmol) of 2,6-dibromophenol with 7.35 g (91.3 mmol) of chloromethylmethyl ether, 22.50 g (100%) of the expected product are obtained in theform of a colourless oil.

¹H NMR (CDCl₃) δ 3.73 (s, 3H), 5.18 (s, 2H), 6.88 (t, 1H, J=8.1 Hz),7.52 (d, 2H, J=8.0 Hz).

(b)6-(3-Bromo-2-methoxymethoxyphenyl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene

In a manner similar to that of Example 1(d), by reaction of 21.72 g(73.4 mmol) of the compound obtained in Example 29(a) with 18.74 g (80.7mmol) of the boronic acid obtained in Example 1(a), 4.04 g (14%) of theexpected product are obtained in the form of a white solid with amelting point of 74° C.

¹H NMR (CDCl₃) δ 1.30 (s, 12H), 1.71 (s, 4H), 3.11 (s, 3H), 4.73 (s,2H), 7.04 (t, 1H, J=7.8 Hz), 7.23 (dd, 1H, J=8.1/1.8 Hz), 7.28 (dd, 1H,J=7.9/1.6 Hz), 7.34 (d, 1H, J=8.1 Hz), 7.45 (d, 1H, J=1.8 Hz), 7.53 (dd,1H, J=7.9/1.6 Hz.

(c)2-Methoxymethoxy-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylboronicacid

In a manner similar to that of Example 1(a), starting with 4.04 g (10.0mmol) of the compound obtained in Example 29(b), 3.82 g (100%) of theexpected product are obtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.30 (s, 6H), 1.32 (s, 6H), 1.72 (s, 4H), 3.26 (s, 3H),4.58 (s, 2H), 6.13 (s, 2H), 7.21 to 7.27 (m, 3H), 7.31 to 7.40 (m, 1H),7.44 to 7.52 (m, 1H), 7.80 (dd, 1H, J=7.3/1.8 Hz).

(d) Ethyl2′-methoxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 1(d), by reaction of 3.82 g (10.4mmol) of the compound obtained in Example 29(c) with 2.20 g (8.0 mmol)of ethyl 4-iodobenzoate, 3.28 g (87%) of the expected product areobtained in the form of a white crystalline solid with a melting pointof 75° C.

¹H NMR (CDCl₃) δ 1.32 (s, 6H), 1.33 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.72 (s, 4H), 2.60 (s, 3H), 4.33 (s, 2H), 4.41 (q, 2H, J=7.2 Hz), 7.29to 7.53 (m, 6H), 7.70 (d, 2H, J=8.4 Hz), 8.11 (d, 2H, J=8.4 Hz).

(e)2′-Methoxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.00 g (2.1mmol) of the ester obtained in Example 29(d), 500 mg (53%) of2′-methoxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 176° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.72 (s, 4H), 2.61 (s, 3H),4.35 (s, 2H), 7.24 to 7.35 (m, 4H), 7.41 (dd, 1H, J=7.3/2.3 Hz), 7.54(s, 1H), 7.75 (d, 2H, J=8.4 Hz), 8.19 (d, 2H, J=8.4 Hz).

Example 30 2′-Hydroxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl)-4-carboxylic acid(a) Ethyl2′-hydroxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 16(a), starting with 2.28 g (4.82mmol) of the compound obtained in Example 29(d), 1.59 g (77%) of theexpected product are obtained in the form of a white solid with amelting point of 121° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.41 (t, 3H, J=7.1 Hz),1.73 (s, 4H), 4.40 (q, 2H, J=7.1 Hz), 5.53 (s, 1H), 7.07 (t, 1H, J=7.6Hz), 7.74 to 7.32 (m, 3H), 7.42 to 7.45 (m, 2H), 7.69 (d, 2H, J=8.4 Hz),8.12 (d, 2H, J=8.4 Hz).

(b)2′-Hydroxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 700 mg (1.6mmol) of the ester obtained in Example 30(a), 526 mg (81%) of2′-hydroxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 232° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.33 (s, 6H), 1.73 (s, 4H), 5.58 (br s,1H), 7.08 (t, 1H, J=7.6 Hz), 7.24 to 7.35 (m, 3H), 7.43 to 7.46 (m, 2H),7.74 (d, 2H, J=8.4 Hz), 8.20 (d, 2H, J=8.3 Hz).

Example 312′-Methoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Ethyl2′-methoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 7(a), by reaction of 890 mg (2.1mmol) of the compound obtained in Example 30(a) with 190 μl (3.1 mmol)of methyl iodide, 800 mg (87%) of the expected product are obtained inthe form of a colourless oil.

¹H NMR (CDCl₃) δ 1.32 (s, 12H), 1.42 (t, 3H, J=7.1 Hz), 1.72 (s, 4H),3.20 (s, 3H), 4.41 (q, 2H, J=7.1 Hz), 7.23 to 7.35 (m, 4H), 7.39 (dd,1H, J=7.3/2.1 Hz), 7.56 (d, 1H, J=1.4 Hz), 7.69 (d, 2H, J=8.3 Hz), 8.11(d, 2H, J=8.3 Hz).

(b)2′-Methoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 800 mg (1.8mmol) of the ester obtained in Example 31(a), 502 mg (67%) of2′-methoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 205° C.,

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.73 (s, 4H), 7.25 to 7.36 (m, 4H), 7.41(dd, 1H, J=7.4/2.0 Hz), 7.57 (d, 1H, J=1.2 Hz), 7.74 (d, 2H, J=8.4 Hz),8.20 (d, 2H, J=8.4 Hz).

Example 323′-Methoxymethoxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Methyl3-bromo-5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)benzoate.

In a manner similar to that of Example 1 (d), by reaction of 7.35 g(21.6 mmol) of methyl 3-bromo-5-iodobenzoate with 7.44 g (32.4 mmol) ofthe boronic acid obtained in Example 1(a), 5.12 g (59%) of the expectedproduct are obtained in the form of a white powder with a melting pointof 88° C.

¹H NMR (CDCl₃) δ 1.32 (s, 6H), 1.35 (s, 6H), 1.72 (s, 4H), 3.95 (s, 3H),7.34 (dd, 1H, J=8.2/1.9 Hz), 7.40 (d, 1H, J=8.2 Hz), 7.48 (d, 1H, J=1.7Hz), 7.87 (t, 1H, J=1.8 Hz), 8.11 (t, 1H, J=1.6 Hz), 8.16 (t, 1H, J=1.5Hz).

(b) 3-Bromo-5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)benzoicacid

In a manner similar to that of Example 1(e), starting with 4.92 g (12.3mmol) of the ester obtained in Example 32(a), 3.26 g (70%) of theexpected product are obtained in the form of a white powder with amelting point of 165° C.

¹H NMR (CDCl₃) δ 1.33 (s, 6H), 1.36 (s, 6H), 1.73 (s, 4H), 7.35, (dd,1H, J=8.2/1.8 Hz), 7.39 (d, 1H, J=8.2 Hz), 7.50 (d, 1H, J=1.7 Hz), 7.94(t, 1H, J=1.7 Hz), 8.20 (t, 1H, J=1.6 Hz), 8.24 (t, 1H, J=1.5 Hz).

(c) 3-Bromo-5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)benzylalcohol

2.76 g (0.87 mmol) of the compound obtained in Example 32(b) and 60 mlof THF are introduced into a round-bottomed flask. The solution obtainedis cooled to 0° C. and 13.75 ml (13.7 mmol) of a solution of borane (1M) in THF are added dropwise and the mixture is stirred for sixteenhours at room temperature and then for two hours at 50° C. Methanol isadded slowly, the mixture is taken up in water and ethyl ether and theorganic phase is separated out after settling has taken place, extractedwith ethyl ether, dried over magnesium sulphate, filtered andevaporated. 2.92 g (100%) of the expected product are collected in theform of a colourless oil.

¹H NMR (CDCl₃) δ 1.30 (s, 6H), 1.33 (s, 6H), 1.71 (s, 4H), 2.60 (br s,1H), 4.68 (s, 2H), 7.28 (dd, 1H, J=8.2/1.9 Hz), 7.36 (d, 1H, J=8.2 Hz),7.45 to 7.47 (m, 3H), 7.60 (s, 1H).

(d)3-Methoxymethoxymethyl-5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)bromobenzene

In a manner similar to that of Example 7(a), by reaction of 2.92 g (7.8mmol) of the bromo alcohol obtained in Example 32(c) with 650 μl (8.6mmol) of chloromethyl methyl ether, 2.52 g (77%) of the expected productare obtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.34 (s, 6H), 1.72 (s, 4H), 3.43 (s, 3H),4.62 (s, 2H), 4.73 (s, 2H), 7.31 (dd, 1H, J=8.2/1.9 Hz), 7.38 (d, 1H,J=8.2 Hz), 7.43 to 7.48 (m, 3H), 7.62 (m, 1H, J=1.9 Hz).

(e)3-Methoxymethoxymethyl-5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylboronicacid

In a manner similar to that of Example 1(a), starting with 2.52 g (6.0mmol) of the compound obtained in Example 32(d), 2.60 g (100%) of theexpected product are obtained in the form of a yellow oil which is usedwithout further purification in the following step.

(f) Ethyl3′-methoxymethoxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 1(d), by reaction of 2.60 g (6.8mmol) of the compound obtained in Example 32(e) with 2.81 g (6.2 mmol)of ethyl 4-iodobenzoate, 1.48 g (45%) of the expected product areobtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.33 (s, 6H), 1.35 (s, 6H), 1.42, (t, 3H, J=7.1 Hz),1.73 (s, 4H), 3.46 (s, 3H), 4.41 (q, 2H, J=7.1 Hz), 4.73 (s, 2H), 4.78(s, 2H), 7.40 (d, 1H, J=0.8 Hz), 7.55 to 7.58 (m, 3H), 7.71 (d, 2H,J=8.4 Hz), 7.73 (s, 1H), 8.14 (d, 2H, J=8.4 Hz).

(g)3′-Methoxymethoxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 600 mg (1.2mmol) of the ester obtained in Example 32(f), 560 mg (99%) of3′-methoxymethoxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 165° C.

¹H NMR (CDCl₃) δ 1.33 (s, 6H), 1.36 (s, 6H), 1.74 (s, 4H), 3.47 (s, 3H),4.75 (s, 2H), 4.79 (s, 2H), 7.41 (s, 2H), 7.56 to 7.60 (m, 3H), 7.74 to7.78 (m, 3H), 8.22 (d, 2H, J=8.3 Hz).

Example 333′-Hydroxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Ethyl3′-hydroxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 16(a), starting with 670 mg (1.4mmol) of the compound obtained in Example 32(f), 380 mg (62%) of theexpected product are obtained in the form of a yellow oil.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 1.33 (s, 6H), 1.36 (s, 6H), 1.73 (s,4H), 4.79 (s, 2H), 7.40 to 7.43 (m, 3H), 7.56 (s, 1H), 7.61 (d, 1H,J=7.4 Hz), 7.69 (s, 1H), 7.73 (d, 2H, J=8.4 Hz), 8.13 (d, 2H, J=8.3 Hz).

(b)3′-Hydroxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 380 mg (0.86mmol) of the ester obtained in Example 33(a), 260 mg (73%) of3′-hydroxymethyl-5′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 213° C.

¹H NMR (DMSO-d₆) δ 1.33 (s, 6H), 1.36 (s, 6H), 1.73 (s, 4H), 4.79 (s,2H), 7.40 to 7.43 (m, 3H), 7.56 (s, 1H), 7.61 (d, 2H, J=7.3 Hz), 7.69(s, 1H), 7.73 (d, 2H, J=8.4 Hz), 8.13 (d, 2H, J=8.3 Hz).

Example 342′-(4,4-Dimethylthiochroman-7-yl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl 3-methoxymethoxybiphenyl-4-carboxylate

In a manner similar to that of Example 1(d), by reaction of 85.00 g(566.7 mmol) of the compound obtained in Example 18(b) with 104.30 g(377.8 mmol) of ethyl 4-iodobenzoate, 162.4 g (100%) of the expectedproduct are obtained in the form of a brown oil.

¹H NMR (CDCl₃) δ 1.42 (t, 3H, J=7.2 Hz), 3.51 (s, 3H), 4.40 (q, 2H,J=7.1 Hz), 5.24 (s, 2H), 7.08 (dt, 1H, J=8.1/1.0 Hz), 7.25 to 7.42 (m,3H), 7.65 (d, 2H, J=8.5 Hz), 8.10 (d, 2H, J=8.5 Hz).

(b) Ethyl 3′-hydroxybiphenyl-4-carboxylate

In a manner similar to that of Example 16(a), starting with 162.00 g(566.7 mmol) of the compound obtained in Example 34(a), 133.41 g (97%)of the expected product are obtained in the form of a beige-colouredpowder with a melting point of 76° C.

¹H NMR (CDCl₃) δ 1.26 (s, 12H), 1.41 (t, 3H, J=7.1 Hz), 4.39 (q, 2H,J=7.1 Hz), 6.88 to 6.91 (m, 1H), 7.09 to 7.13 (m, 2H), 7.25 to 7.33 (m,1H), 7.64 (m, 2H, J=8.3 Hz), 8.08 (d, 2H, J=8.3 Hz), 8.77 (br s, 1H).

(c) 3′-Hydroxybiphenyl-4-carboxylic acid

In a manner similar to that of Example 1(e), starting with 130.00 g(536.6 mmol) of the ester obtained in Example 34(b), 40.00 g (35%) ofthe expected product are obtained in the form of a pale beige powderwith a melting point of 180° C.

¹H NMR (DMSO-d₆) δ 6.50 (dd, 1H, J=7.2/1.5 Hz), 6.71 to 6.74 (m, 2H),7.22 to 7.31 (m, 1H), 7.30 (d, 2H, J=8.3 Hz), 7.71 (d, 2H, J=8.3 Hz).

(d) 4′-Iodo-3′-hydroxybiphenyl-4-carboxylic acid

40.00 g (186.7 mmol) of the compound obtained in Example 34(c), 7.47 g(186.7 mmol) of sodium hydroxide pellets, 27.98 g (186.7 mmol) of sodiumiodide and 800 ml of methanol are introduced into a two-litrethree-necked flask under a stream of nitrogen. The mixture is cooled to0° C. and 111.00 g (186.7 mmol) of aqueous 12.5% sodium hypochloritesolution are added dropwise over one hour and fifty minutes. Thereaction medium is stirred for five hours at 0° C., a sodiumthiosulphate solution is then added, this mixture is acidified to pH 5and extracted with ethyl ether, the organic phase is washed with waterto neutral pH, dried over magnesium sulphate and filtered and thesolvents are evaporated off. 54.00 g (85%) of the expected compound arecollected in the form of a rust-coloured powder with a melting point of174° C.

¹H NMR (DMSO-d₆) δ 6.83 to 6.89 (m, 1H), 7.11 to 7.24 (m, 1H), 7.38 to7.41 (m, 1H), 7.60 to 7.76 (m, 2H), 8.06 to 8.17 (m, 2H).

(e) Methyl 4′-iodo-3′-hydroxybiphenyl-4-carboxylate

In a manner similar to that of Example 1(b), starting with 54.00 g(158.8 mmol) of the compound obtained in Example 34(d), 27.16 g (48%) ofthe expected product are obtained in the form of a pale beige powderwith a melting point of 192° C.

¹H NMR (DMSO-d₆) δ 3.44 (s, 3H), 6.37 (dd, 1H, J=8.1/2.1 Hz), 6.70 (d,1H, J=2.0 Hz), 7.13 (d, 2H, J=8.5 Hz), 7.26 (d, 1H, J=8.1 Hz), 7.58 (d,2H, J=8.4 Hz), 9.45 (br s, 1H).

(f) Methyl 2′-hydroxy-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 1(d), by reaction of 27.16 g(76.6 mmol) of the compound obtained in Example 34(e) with 14.03 g(115.0 mmol) of phenylboronic acid, 2.90 g (12%) of the expected productare obtained in the form of a yellow oil.

¹H NMR (DMSO-d₆) δ 3.88 (s, 3H), 7.25 to 7.45 (m, 6H), 7.61 (d, 2H,J=7.1 Hz), 7.79 (d, 2H, J=8.3 Hz), 8.06 (d, 2H, J=8.3 Hz), 9.85 (br s,1H).

(g) Methyl2′-trifluoromethanesulphonyloxy-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(a), starting with 2.90 g (9.5mmol) of the compound obtained in Example 34(d), 3.62 mg (87%) of theexpected product are obtained in the form of a beige-coloured powderwith a melting point of 95° C.

¹H NMR (CDCl₃) δ 3.96 (s, 3H), 7.41 to 7.72 (m, 10H), 8.16 (d, 2H, J=8.5Hz).

(h) 1-Bromo-3-(3-methylbut-2-enylsulphanyl)benzene

25.00 g (132.0 mmol) of 3-bromothiophenol, 200 ml of DMF and 18.23 g(138.0 mmol) of potassium carbonate are introduced into a three-neckedflask. 18.0 ml (157.0 mmol) of 1-bromo-3-methyl-2-butene are addeddropwise and the mixture is stirred at room temperature for five hours.The reaction medium is poured into water and extracted with ethylacetate, and the organic phase is separated out after settling has takenplace, washed with water, dried over magnesium sulphate and evaporated.33.00 g (97%) of the expected compound are collected in the form of ayellow oil.

¹H NMR (CDCl₃) δ 1.62 (s, 3H), 1.73 (s, 3H), 3.54, (d, 2H, J=7.7 Hz),5.28 (t, 1H, J=7.7 Hz), 7.09 to 7.15 (m, 1H), 7.22 to 7.31 (m, 2H), 7.45(s, 1H).

(i) 7-Bromo-4,4-dimethylthiochroman

25.00 g (97.0 mmol) of 1-bromo-3-(3-methylbut-2-enylsulphonyl)benzene,200 ml of toluene and 27.75 g (146.0 mmol) of para-toluenesulphonic acidare introduced into a three-necked flask. The reaction medium isrefluxed for four hours and evaporated to dryness. The residue is takenup in aqueous sodium hydrogen carbonate solution and extracted withethyl acetate, and the organic phase is separated out after settling hastaken place, dried over magnesium sulphate and evaporated. The residueobtained is purified by chromatography on a column of silica eluted withheptane. 22.57 g (90%) of the expected compound are obtained in the formof a yellow oil.

¹H NMR (CDCl₃) δ 1.23 (s, 6H), 1.84 to 1.89 (m, 2H), 2.92 to 2.97 (m,2H), 7.03 (dd, 1H, J=8.5/2.0 Hz), 7.13 (d, 1H, J=2.0 Hz).

(j) 7-Bromo-4,4-dimethylthiochromanboronic acid

In a manner similar to that of Example 1(a), starting with 5.00 g (20.4mmol) of the compound obtained in Example 34(i), 2.63 g (61%) of theexpected product are obtained in the form of a pale beige solid with amelting point of 242° C.

¹H NMR (CDCl₃) δ 1.37 (s, 6H), 1.98 to 2.02 (m, 2H), 3.05 to 3.10 (m,2H), 7.48 (d, 1H, J=7.9 Hz), 7.82 (dd, 1H, J=7.9/1.2 Hz), 7.89 (d, 1H,J=1.0 Hz).

(k) Methyl2′-(4,4-dimethylthiochroman-7-yl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(b), by reaction of 1.81 g (4.1mmol) of the compound obtained in Example 34(g) with 1.04 g (5.0 mmol)of the boronic acid obtained in Example 34(j), 570 mg (30%) of theexpected product are obtained in the form of a white solid with amelting point of 172° C.

¹H NMR (CDCl₃) δ 1.29 (s, 6H), 1.95 (t, 2H, J=5.9 Hz), 3.02 (t, 2H,J=5.9 Hz), 3.95 (s, 3H), 6.69 (dd, 1H, J=8.1/1.8 Hz), 7.04 (d, 1H, J=1.8Hz), 7.14 (d, 1H, J=8.2 Hz), 7.19 to 7.26 (m, 5H), 7.50 (d, 1H, J=8.5Hz), 7.65 to 7.67 (m, 2H), 7.73 (d, 2H, J=8.4 Hz), 8.12 (d, 2H, J=8.3Hz).

(l)2′-(4,4-Dimethylthiochroman-7-yl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 570 mg (1.2mmol) of the ester obtained in Example 34(k), 500 mg (90%) of2′-(4,4-dimethylthiochroman-7-yl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 261° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 0.64 (s, 6H), 1.53 (t, 2H, J=5.9Hz), 2.65 (5, 2H, J=6.0 Hz), 6.63 (d, 1H, J=1.6 Hz), 6.71 (d, 1H, J=8.0Hz), 6.77 (dd, 1H, J=8.1/1.7 Hz), 6.84 to 6.97 (m, 5H), 7.19 (d, 1H,J=8.6 Hz), 7.32 to 7.36 (m, 2H), 7.42 (d, 2H, J=8.3 Hz), 7.81 (d, 2H,J=8.3 Hz)

Example 352′-(4,4-Dimethylthiochroman-6-yl)-[1,1′;4′,1″]-terphenyl-4″-carboxylicacid (a) 1-Bromo-4-(3-methylbut-2-enylsulphanyl)benzene

In a manner similar to that of Example 34(h), by reaction of 30.00 g(159.0 mmol) of 4-bromo-thiophenol with 26.00 g (175.0 mmol) of1-bromo-3-methyl-2-butene, 37.40 g (93%) of the expected product areobtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.59 (s, 3H), 1.71 (s, 3H), 3.51 (d, 2H, J=7.7 Hz),5.27 (t, 1H, J=7.7 Hz), 7.19 (d, 2H, J=8.5 Hz), 7.38 (d, 2H, J=8.5 Hz).

(b) 6-Bromo-4,4-dimethylthiochroman

In a manner similar to that of Example 34(i), starting with 34.00 g(132.0 mmol) of the compound obtained in Example 35(a), 21.80 g (64%) ofthe expected product are obtained in the form of a brown solid with amelting point of 51° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.93 (t, 2H, J=6.0 Hz), 3.01 (t, 2H,J=6.1 Hz), 6.94 (d, 1H, J=8.4 Hz), 7.13 (dd, 1H, J=8.4/2.2 Hz), 7.45 (d,1H, J=2.1 Hz).

(c) 6-Bromo-4,4-dimethylthiochromanboronic acid

In a manner similar to that of Example 1(a), starting with 5.00 g (20.4mmol) of the compound obtained in Example 35(b), 2.28 g (53%) of theexpected product are obtained in the form of a white solid with amelting point of 242° C.

¹H NMR (CDCl₃) δ 1.43 (s, 6H), 1.98 to 2.04 (m, 2H), 3.06 to 3.11 (m,2H), 7.21 (d, 1H, J=7.8 Hz), 7.81 (dd, 1H, J=7.8/1.1 Hz), 8.20 (d, 1H,J=1.1 Hz).

(d) Methyl2′-(4,4-dimethylthiochroman-6-yl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(b), by reaction of 1.81 g (4.1mmol) of the compound obtained in Example 34(g) with 1.04 g (5.0 mmol)of the boronic acid obtained in Example 35(c), 680 mg (35%) of theexpected product are obtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.27 (s, 6H), 1.83 to 1.88 (m, 2H), 2.94 to 2.99 (m,2H), 3.94 (s, 3H), 6.96 (d, 1H, J=1.4 Hz), 7.04 to 7.25 (m, 7H), 7.51(d, 1H, J=7.9 Hz), 7.65 (dd, 1H, J=7.9/2.0 Hz), 7.69 (d, 1H, J=1.8 Hz),7.73 (d, 2H, J=8.5 Hz), 8.13 (d, 2H, J=8.5 Hz).

(e)2′-(4,4-Dimethylthiochroman-6-yl)-[1,1′;4′,1″]-terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 680 mg (1.5mmol) of the ester obtained in Example 35(d), 280 mg (42%) of2′-(4,4-dimethylthio-croman-6-yl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 279° C.

¹H NMR (CDCl₃) δ 1.29 (s, 6H), 1.95 (t, 2H, J=5.9 Hz), 3.01 (t, 2H,J=5.9 Hz), 6.70 (dd, 1H, J=8.2/1.9 Hz), 7.01 (d, 1H, J=1.9 Hz), 7.15 (d,1H, J=8.3 Hz), 7.17 to 7.42 (m, 5H), 7.50 (d, 1H, J=8.7 Hz), 7.65 to7.69 (m, 2H), 7.73 (d, 2H, J=8.4 Hz), 8.13 (d, 2H, J=8.4 Hz).

Example 362′-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) 6-Bromo-1,1,4,4,7-pentamethyl-1,2,3,4-tetrahydronaphthalene

18.31 g (100.0 mmol) of 2,5-dichloro-2,5-dimethylhexane, 17.10 g (100.0mmol) of 2-bromotoluene and 200 ml of 1,2-dichloroethane are introducedinto a three-necked flask under an argon atmosphere. 1.33 g (10.0 mmol)of aluminium chloride are added rapidly in a single portion and thereaction medium is stirred for thirty minutes at room temperature. Thereaction medium is poured into water, extracted with dichloromethane andwashed with water, and the organic phase is separated out after settlinghas taken place, dried over magnesium sulphate and evaporated. Afterrecrystallization of the residue from methanol, 17.78 g (63%) of theexpected compound are collected in the form of fine white crystals witha melting point of 73° C.

¹H NMR (CDCl₃) δ 1.25 (s, 12H), 1.65 (s, 4H), 2.33 (s, 3H), 7.14 (s,1H), 7.42 (s, 1H).

(b) 5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthylboronic acid

In a manner similar to that of Example 1(a), starting with 14.00 g (49.8mmol) of the compound obtained in Example 36(a), 7.36 mg (60%) of theexpected product are obtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.32 (s, 6H), 1.34 (s, 6H), 1.72 (s, 4H), 2.81 (s, 3H),7.21 (s, 1H), 8.28 (s, 1H).

(c) Ethyl4-[4-hydroxy-3-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 1(d), by reaction of 2.26 g (7.0mmol) of the compound obtained in Example 1(c) with 2.08 g (8.4 mmol) ofthe boronic acid obtained in Example 36(b), 1.00 g (32%) of the expectedproduct is obtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.27 (s, 6H), 1.33 (s, 6H), 1.41 (t, 3H, J=7.1 Hz),1.71 (s, 4H), 2.17 (s, 3H), 4.39 (q, 2H, J=7.1 Hz), 5.05 (s, 1H), 7.09(d, 1H, J=8.4 Hz), 7.21 (s, 1H), 7.25 (s, 1H), 7.45 (d, 1H, J=2.3 Hz),7.56 (dd, 1H, J=8.4/2.3 Hz), 7.64 (d, 2H, J=8.4 Hz), 8.08 (d, 2H, J=8.4Hz).

(d) Ethyl3′-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-4′-trifluoromethanesulphonyloxybiphenyl-4-carboxylate

In a manner similar to that of Example 13(a), starting with 1.00 g (2.3mmol) of the ester obtained in Example 36(c), 1.30 g (100%) of theexpected product are obtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.26 (d, 6H, J=6.8 Hz), 1.31 (d, 6H, J=6.5 Hz), 1.42(t, 3H, J=7.1 Hz), 1.71 (s, 4H), 2.15 (s, 3H), 4.40 (q, 2H, J=7.1 Hz),7.16 (s, 1H), 7.21 (s, 1H), 7.43 to 7.47 (m, 1H), 7.64 to 7.68 (m, 2H),7.67 (d, 2H, J=8.4 Hz), 8.13 (d, 2H, J=8.4 Hz).

(e) Ethyl2′-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(b), by reaction of 1.00 g (1.7mmol) of the compound obtained in Example 36(d) with 254 mg (2.1 mmol)of benzeneboronic acid, 770 mg (88%) of the expected product areobtained in the form of a colourless oil which is used directly in thefollowing step.

(f)2′-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 770 mg (1.5mmol) of the ester obtained in Example 36(e), 150 mg (21%) of2′-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a beige-coloured powder with a meltingpoint of 217° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 1.20 (s, 6H), 1.26 (s, 6H), 1.63 (s,4H), 2.11 (s, 3H), 6.28 (br s, 1H), 6.83 to 7.16 (m, 5H), 7.23 (s, 1H),7.37 (d, 1H, J=2.2 Hz), 7.47 (dd, 1H, J=8.4/2.4 Hz), 7.57 (d, 2H, J=8.4Hz), 8.02 (d, 2H, J=8.3 Hz).

Example 372′-(3-Methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) 3-Bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthol

In a manner similar to that of Example 36(a), by reaction of 67.14 g(388.0 mmol) of 2-bromophenol with 71.10 g (388.0 mmol) of2,5-dichloro-2,5-dimethylhexane, 86.13 g (78%) of the expected productare obtained in the form of a white solid with a melting point of 90–94°C.

¹H NMR (CDCl₃) δ 1.16 (s, 6H), 1.17 (s, 6H), 1.57 (s, 4H), 5.21 (s, 1H),6.87 (s, 1H), 7.26 (s, 1H).

(b)6-Bromo-7-methoxymethoxy-1-1-4-4-tetramethyl-1,2,3,4-tetrahydronaphthalene

In a manner similar to that of Example 7(a), by reaction of 8.00 g (28.2mmol) of the compound obtained in Example 37(a) with 2.36 ml (31.1 mmol)of chloromethyl methyl ether, 9.49 g (100%) of the expected product areobtained in the form of a beige-coloured oil.

¹H NMR (CDCl₃) δ 1.24 (s, 6H), 1.26 (s, 6H), 1.65 (s, 4H), 3.53 (s, 3H),5.20 (s, 2H), 7.06 (s, 1H), 7.42 (s, 1H).

(c)3-Methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylboronicacid

In a manner similar to that of Example 1(a), starting with 9.49 g (29.0mmol) of the compound obtained in Example 37(b), 8.21 g (97%) of theexpected product are obtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.12 (s, 12H), 1.51 (s, 4H), 3.34 (s, 3H), 5.10 (s,2H), 6.40 (s, 2H), 6.88 (s, 1H), 7.64 (s, 1H).

(d) Ethyl4-[4-hydroxy-3-(3-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

In a manner similar to that of Example 1(d), by reaction of 8.10 g (25.2mmol) of the compound obtained in Example 1(c) with 6.15 g (21.0 mmol)of the boronic acid obtained in Example 37(c), 5.26 g (51%) of theexpected product are obtained in the form of a pale yellow oil.

¹H NMR (CDCl₃) δ 1.21 (s, 6H), 1.25 (s, 6H), 1.33 (t, 3H, J=7.1 Hz),1.63 (s, 4H), 3.31 (s, 3H), 4.31 (q, 2H, J=7.1 Hz), 5.06 (s, 2H), 6.31(s, 1H), 7.00 (d, H, J=8.3 Hz), 7.09 (s, 1H), 7.20 (s, 1H), 7.45 to 7.48(dd, 1H, J=8.3/2.3 Hz), 7.51 (d, 1H, J=2.3 Hz), 7.57 (d, 2H, J=8.4 Hz),8.01 (d, 2H, J=8.4 Hz).

(e) Ethyl3′-(3-methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-4′-trifluoromethane-sulphonyloxybiphenyl-4-carboxylate

4.76 g (9.7 mmol) of the ethyl ester obtained in Example 37(d), 2.64 g(9.7 mmol) of 4-nitrophenyl triflate, 2.64 g (1.9 mmol) of potassiumcarbonate and 100 ml of 1,2-dimethoxyethane are introduced into athree-necked flask under a stream of nitrogen. The reaction medium isstirred at room temperature for three hours and poured into a mixture ofwater and ethyl ether, and the organic phase is separated out aftersettling has taken place, extracted with ethyl ether, washed with wateruntil the 4-nitrophenol has disappeared from the aqueous phase, driedover magnesium sulphate and evaporated. 6.05 g (100%) of the expectedproduct are collected in the form of a beige-coloured oil.

¹H NMR (CDCl₃) δ 1.26 (t, 3H, J=7.1 Hz), 1.27 (s, 6H), 1.32 (s, 6H),1.72 (s, 4H), 3.37 (s, 3H), 3.41 (q, 2H, J=7.1 Hz), 5.10 (s, 2H) 7.17(s, 1H), 7.19 (s, 1H), 7.42 (d, 1H, J=8.5 Hz), 7.62 to 7.71 (m, 4H),8.13 (d, 2H, J=8.4 Hz).

(f) Ethyl2′-(3-methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(b), by reaction of 6.59 g(10.6 mmol) of the compound obtained in Example 37(e) with 1.55 g (12.7mmol) of benzeneboronic acid, 5.30 g (91%) of the expected product areobtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 1.26 (s, 6H), 1.27 (s, 6H), 1.30 (t, 3H, J=7.1 Hz),1.60 to 1.64 (m, 4H), 3.22 (s, 3H), 4.41 (q, 2H, J=7.1 Hz), 4.75 (br s,2H) 6.93 (s, 1H), 7.02 (s, 1H), 7.16 to 7.19 (m, 2H), 7.44 (d, 1H, J=8.5Hz), 7.55 (d, 1H, J=8.0 Hz), 7.62 to 7.77 (m, 6H), 8.13 (d, 2H, J=7.6Hz).

(g)2′-(3-Methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 1.00 g (1.8mmol) of the ester obtained in Example 37(f), 540 mg (57%) of2′-(3-methoxymethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 219–222° C.

¹H NMR (CDCl₃) δ 1.03 (br s, 6H), 1.26 (s, 6H), 1.58 to 1.66 (m, 4H),3.21 (s, 3H), 4.75 (br s, 2H), 6.93 (s, 1H), 7.01 (s, 1H), 7.16 to 7.21(m, 5H), 7.55 (d, 1H, J=8.0 Hz), 7.68 (dd, 1H, J=8.0/1.9 Hz), 7.72 (s,1H) 7.74 (d, 2H, J=8.4 Hz), 8.14 (d, 2H, J=8.4 Hz).

Example 382′-(3-Hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl2′-(3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 16(a), starting with 4.30 g (7.8mmol) of the compound obtained in Example 37(f), 1.65 g (42%) of theexpected product are obtained in the form of a white powder with amelting point of 145° C.

¹H NMR (CDCl₃) δ 0.98 (s, 6H), 1.24 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.56 to 1.64 (m, 4H), 4.41 (q, 2H, J=7.1 Hz), 4.76 (s, 1H), 6.80 (d, 2H,J=7.8 Hz), 7.13 to 7.23 (m, 5H), 7.62 (d, 1H, J=7.9 Hz), 7.72 to 7.73(m, 1H), 7.74 (d, 2H, J=8.4 Hz), 8.13 (d, 2H, J=8.4 Hz).

(b)2′-(3-Hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 600 mg (1.1mmol) of the ester obtained in Example 38(a), 400 mg (70%) of2′-(3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 273° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 0.91 (s, 6H), 1.23 (s, 6H), 1.53 to1.61 (m, 4H), 6.70 (s, 1H), 6.79 (s, 1H), 7.13 to 7.18 (m, 5H), 7.54 (d,1H, J=8.0 Hz), 7.66 (dd, 1H, J=8.0/1.9 Hz), 7.74 (d, 2H, J=8.3 Hz), 7.82(d, 1H, J=1.8 Hz), 8.10 (d, 2H, J=8.3 Hz), 8.18 (br s, 1H).

Example 392′-(3-Methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[(1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl2′-(3-methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 7(a), by reaction of 530 mg (1.1mmol) of the compound obtained in Example 38(a) with 71 μl (1.1 mmol) ofmethyl iodide, 544 mg (100%) of the expected product are obtained in theform of a colourless oil.

¹H NMR (CDCl₃) δ 1.04 (s, 6H), 1.27 (s, 6H), 1.42 (t, 3H, J=7.1 Hz),1.59 to 1.67 (m, 4H), 3.48 (s, 3H), 4.40 (q, 2H, J=7.1 Hz), 6.68 (s,1H), 6.94 (s, 1H), 7.10 to 7.19 (m, 5H), 7.54 (d, 1H, J=8.0 Hz), 7.67(dd, 1H, J=8.0/2.0 Hz), 7.73 to 7.74 (m, 1H), 7.75 (d, 2H, J=8.4 Hz),8.12 (d, 2H, J=8.4 Hz).

(b)2′-(3-Methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1;4′,1″]terphenyl-41″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 544 mg (1.0mmol) of the ester obtained in Example 39(a), 490 mg (95%) of2′-(3-methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 248° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 1.04 (s, 6H), 1.27 (s, 6H), 1.59 to1.67 (m, 4H), 3.48 (s, 3H), 6.67 (s, 1H), 6.93 (s, 1H), 7.10 to 7.18 (m,5H), 7.54 (d, 1H, J=8.0 Hz), 7.67 (dd, 1H, J=8.0/2.0 Hz), 7.73 (d, 2H,J=8.3 Hz), 7.74 (s, 1H), 8.13 (d, 2H, J=8.3 Hz).

Example 402′-(3-Propyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Ethyl2′-(3-propyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″carboxylate

In a manner similar to that of Example 7 (a), by reaction of 450 mg (8.3mmol) of the compound obtained in Example 38(a) with 89 μl (9.2 mmol) ofpropyl iodide, 450 mg (92%) of the expected product are obtained in theform of a yellow solid with a melting point of 163° C., which is useddirectly in the following step.

(b)2′-(3-Propyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 450 mg (0.8mmol) of the ester obtained in Example 40(a), 400 mg (94%) of2′-(3-propyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 234° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 0.85 (t, 3H, J=7.5 Hz), 0.95 (br s,6H), 1.27 (s, 6H), 1.54 to 1.70 (m, 6H), 3.72, (t, 2H, J=6.6 Hz), 6.73(s, 1H), 6.82 (s, 1H), 7.11 to 7.17 (m, 5H), 7.53 (d, 1H, J=8.0 Hz),7.66 (dd, 1H, J=8.0/1.9 Hz), 7.74 (d, 2H, J=8.4 Hz), 7.79 (d, 1H, J=1.8Hz), 8.13 (d, 2H, J=8.3 Hz).

Example 413′-Methyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) 2-Bromo-4-nitrophenol

139.40 g (64.7 mmol) of 4-nitrophenol and 130 ml of dichloromethane areintroduced into a three-necked flask under an argon atmosphere. Themixture is cooled to 0° C. and 3.31 ml (67.7 mmol) of bromine are addeddropwise. The reaction medium is stirred for one hour at 0° C., 360 mg(6.5 mmol) of iron powder are then added and this mixture is stirred forsixteen hours at room temperature. The reaction medium is poured intowater, a saturated sodium thiosulphate solution is added, this mixtureis extracted with dichloromethane and washed with water, the organicphase is separated out after settling has taken place and dried overmagnesium sulphate, and the solvents are evaporated off. 13.50 g (96%)of the expected compound are collected in the form of a beige-colouredpowder with a melting point of 105–107° C.

¹H NMR (CDCl₃) δ 6.34 (br s, 1H), 7.13 (d, 1H, J=9.0 Hz), 8.16 (dd, 1H,J=9.1/2.7 Hz), 8.44 (d, 1H, J=2.7 Hz).

(b) 4-Nitro-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)phenol

In a manner similar to that of Example 1(d), by reaction of 160.00 g(672.0 mmol) of the boronic acid obtained in Example 1(a) with 100.00 g(459.0 mmol) of the compound obtained in Example 41(a), 81.70 g (55%) ofthe expected compound are obtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.25 (s, 6H), 1.26 (s, 6H), 1.67 (s, 4H), 5.89 (br s,1H), 7.00 (d, 1H, J=9.7 Hz), 7.13 (dd, 1H, J=8.1/1.9 Hz), 7.28 (d, 1H,J=1.9 Hz), 7.41 (d, 1H, J=8.1 Hz), 8.07 to 8.11 (m, 2H).

(c) 4-Nitro-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyltrifluoromethylsulphonate

In a manner similar to that of Example 13(a), starting with 78.50 g(241.0 mmol) of the compound obtained in Example 41(b), 81.40 g (73%) ofthe expected product are obtained in the form of a grey powder with amelting point of 87–89° C.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.32 (s, 6H), 1.73 (s, 4H), 7.21 (dd, 1H,J=8.2/2.0 Hz), 7.39 (d, 1H, J=1.9 Hz), 7.44 (d, 1H, J=8.2 Hz), 7.56 (d,1H, J=9.0 Hz), 8.27 (dd, 1H, J=9.0/2.9), 8.37 (d, 1H, J=2.8 Hz).

(d)1,1,4,4-Tetramethyl-6-(4-nitrobiphenyl-2-yl)-1,2,3,4-tetrahydronaphthalene

In a manner similar to that of Example 13 (b), by reaction of 81.00 g(177.0 mmol) of the compound obtained in Example 41(c) with 32.20 g(265.0 mmol) of phenylboronic acid, 62.20 g (265.0 g) of the expectedproduct are obtained in the form of a beige-coloured powder with amelting point of 181–183° C.

¹H NMR (CDCl₃) δ 0.90 (s, 6H), 1.26 (s, 6H), 1.56 to 1.64 (m, 4H), 6.84(d, 1H, J=1.9 Hz), 7.09 to 7.15 (m, 3H), 7.25 to 7.30 (m, 4H), 7.56 (d,1H, J=8.4 Hz), 8.21 (dd, 1H, J=8.5/2.4 Hz), 8.32 (d, 1H, J=2.4 Hz).

(e)2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-ylamine

62.00 g (160.0 mmol) of the compound obtained in Example 41(d) and onelitre of methanol are introduced into a two-litre hydrogenator. Thesystem is flushed with nitrogen, 1.85 g of 5% palladium on charcoal areadded, the system is flushed with hydrogen and the reaction medium isstirred for six hours at 60° C. under a pressure of seven bar ofhydrogen. After cooling the reaction medium and filtration throughCelite®, the solvents are evaporated off and the product is purified bychromatography on a column of silica eluted with a mixture composed of80% heptane and 20% ethyl acetate. After evaporation of the solvents,43.00 g (75%) of the expected compound are collected in the form of anorange-coloured oil.

¹H NMR (CDCl₃) δ 1.25 (s, 12H), 1.53 to 1.63 (m, 4H), 3.74 (br s, 2H),6.72 (dd, 1H, J=8.1/2.5 Hz), 6.79 (d, 1H, J=2.4 Hz), 6.86 (d, 1H, J=1.9Hz), 7.04 to 7.24 (m, 8H).

(f)6-(4-Iodobiphenyl-2-yl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene

40.00 g (113.0 mmol) of the compound obtained in Example 41(e) and 113ml (113 mmol) of a 1 M solution of diiodomethane are introduced into a500 ml round-bottomed flask under an argon atmosphere. 45.5 ml ofisoamyl nitrite are added dropwise and the reaction mixture is heated at60° C. for twenty minutes. After evaporation to dryness, the product ispurified by chromatography on a column of silica eluted with a mixturecomposed of 90% heptane and 10% ethyl acetate. After evaporation of thesolvents, 21.00 g (40%) of the expected compound are collected in theform of an off-white powder with a melting point of 120–122° C.

¹H NMR (CDCl₃) δ 0.89 (s, 6H), 1.25 (s, 6H), 1.54 to 1.62 (m, 4H), 6.80(d, 1H, J=1.9 Hz), 7.03 to 7.24 (m, 8H), 7.70 (dd, 1H, J=8.1/1.9 Hz),7.80 (d, 1H, J=1.8 Hz).

(g)3-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-4-phenylbenzeneboronicacid

In a manner similar to that of Example 1(a), starting with 18.00 g (38.0mmol) of the compound obtained in Example 41(f), 11.90 g (81%) of theexpected product are obtained in the form of a pink-white solid with amelting point of 257–259° C.

¹H NMR (CDCl₃) δ 0.93 (s, 6H), 1.28 (s, 6H), 1.58 to 1.63 (m, 4H), 6.92(d, 1H, J=1.7 Hz), 7.20 to 7.31 (m, 7H), 7.56 (d, 1H, J=7.6 Hz), 8.28(dd, 1H, J=8.7/1.1 Hz), 8.34 (s, 1H).

(h) Methyl3″-methyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 1(d), by reaction of 700 mg (1.8mmol) of the compound obtained in Example 41(g) with 380 mg (1.7 mmol)of methyl 2-methyl-4-bromobenzoate, 740 mg (91%) of the expected productare obtained in the form of a white solid with a melting point of130–132° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.54 to 1.64 (m, 4H), 2.68(s, 3H), 3.92 (s, 3H), 6.89 (d, 1H, J=1.7 Hz), 7.15 to 7.29 (m, 7H),7.50 to 7.56 (m, 3H), 7.65 (dd, 1H, J=7.9/1.8 Hz), 7.72 (d, 1H, J=1.7Hz), 8.02 (d, 1H, J=8.7 Hz).

(i)3″-Methyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 700 mg (1.4mmol) of the ester obtained in Example 41(h), 537 mg (79%) of3″-methyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 237–239° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.57 to 1.65 (m, 4H), 2.75(s, 3H), 6.90 (d, 1H, J=1.8 Hz), 7.15 to 7.30 (m, 7H), 7.53 (d, 1H,J=7.9 Hz), 7.59 to 7.61 (m, 2H), 7.66 (dd, 1H, J=8.0/1.9 Hz), 7.74 (d,1H, J=1.8 Hz), 8.19 (d, 1H, J=8.7 Hz).

Example 422″-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) 3-Hydroxy-4-iodobenzoic acid

25.00 g (180.0 mmol) of 3-hydroxybenzoic acid, 7.20 g (180.0 mmol) ofsodium hydroxide pellets, 27.13 g (180.0 mmol) of sodium iodide and 500ml of methanol are introduced into a one-litre three-necked flask undera stream of nitrogen. The mixture is cooled to 0° C. and 374.30 g (180.0mmol) of an aqueous sodium hypochlorite solution are added dropwise overone hour and fifty minutes. The reaction medium is stirred for two hoursat 0° C., a sodium thiosulphate solution is then added, the mixture isacidified at pH 5, extracted with ethyl ether, the organic phase iswashed with water to neutral pH, dried over magnesium sulphate andfiltered and the solvents are evaporated off. 43.80 g (92%) of theexpected compound are collected in the form of a beige-coloured powderwith a melting point of 198° C.

¹H NMR (CDCl₃) δ 7.13 (dd, 1H, J=8.1/1.9 Hz), 7.43 (d, 1H, J=1.8 Hz),7.80 (d, 1H, J=8.1 Hz), 10.69 (br s, 1H), 12.98 (br s, 1H).

(b) Methyl 3-hydroxy-4-iodobenzoate

In a manner similar to that of Example 1(b), starting with 43.80 g(166.0 mmol) of the acid obtained in Example 42(a), 43.54 g (94%) ofmethyl 3-hydroxy-4-iodobenzoate are obtained in the form of abeige-coloured powder with a melting point of 153° C.

¹H NMR (CDCl₃) δ 3.89 (s, 3H), 7.25 (dd, 1H, J=8.2/1.9 Hz), 7.58 (d, 1H,J=1.9 Hz), 7.77 (d, 1H, J=8.2 Hz), 8.79 (br s, 1H).

(c) Methyl2″-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 1(d), by reaction of 2.80 g (7.3mmol) of the boronic acid obtained in Example 41(g) with 1.84 g (6.6mmol) of the compound obtained in Example 42(b), 2.00 g (62%) of theexpected product are obtained in the form of a white solid with amelting point of 183–185° C.

¹H NMR (CDCl₃) δ 0.89 (s, 6H), 1.26 (s, 6H), 1.56 to 1.64 (m, 4H), 3.94(s, 3H), 5.51 (s, 1H), 6.89 (d, 1H, J=1.9 Hz), 7.18 to 7.26 (m, 7H),7.42 (d, 1H, J=8.3 Hz), 7.53 to 7.55 (m, 2H), 7.59 to 7.60 (m, 1H), 7.68to 7.71 (m, 2H)

(d)2″-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 500 mg (1.0mmol) of the ester obtained in Example 42(c), 480 mg (99%) of2″-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 282–284° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 0.90 (s, 6H), 1.25 (s, 6H), 1.55 to1.63 (m, 4H), 6.88 (d, 1H, J=1.5 Hz), 7.12 to 7.25 (m, 7H), 7.43 (d, 1H,J=8.1 Hz), 7.47 (d, 1H, J=8.7 Hz), 7.61 (s, 1H), 7.65 to 7.67 (m, 1H),7.71 (d, 2H, J=7.6 Hz).

Example 432″-Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Methyl2″-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 7(a), by reaction of 580 mg (1.2mmol) of the compound obtained in Example 42(c) with 103 μl (1.3 mmol)of chloromethyl methyl ether, 630 mg (100%) of the expected product areobtained in the form of an orange-coloured oil.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.26 (s, 6H), 1.56 to 1.63 (m, 4H), 3.48(s, 3H), 3.94 (s, 3H), 5.26 (s, 2H), 6.91 (d, 1H, J=1.8 Hz), 7.10 (dd,1H, J=7.9/1.9 Hz), 7.19 to 7.25 (m, 6H), 7.46 to 7.51 (m, 2H), 7.61 (dd,1H, J=7.8/1.7 Hz), 7.65 (d, 1H, J=1.7 Hz), 7.79 (dd, 1H, J=7.9/1.8 Hz),7.89 (d, 1H, J=1.5 Hz).

(b)2″-Methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 620 mg (1.2mmol) of the ester obtained in Example 43(a), 556 mg (92%) of2″-methoxymethoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 204–206° C.

¹H NMR (CDCl₃) δ 0.92 (s, 6H), 1.26 (s, 6H), 1.56 to 1.64 (m, 4H), 3.49(s, 3H), 5.28 (s, 2H), 6.92 (d, 1H, J=1.7 Hz), 7.12 (dd, 1H, J=7.9/1.8Hz), 7.18 to 7.26 (m, 6H), 7.49 (d, 1H, J=7.9 Hz), 7.54 (d, 1H,J=8.0/1.8 Hz), 7.67 (d, 1H, J=1.6 Hz), 7.88 (dd, 1H, J=7.9/1.8 Hz), 7.99(d, 1H, J=1.4 Hz).

Example 442″-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylic acid (a) Methyl2″-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 7(a), by reaction of 500 mg (1.0mmol) of the compound obtained in Example 42(c) with 70 μl (1.1 mmol) ofmethyl iodide, 510 mg (99%) of the expected product are obtained in theform of a pale beige powder with a melting point of 144–146° C.

¹H NMR (CDCl₃) δ 0.90 (s, 6H), 1.26 (s, 6H), 1.56 to 1.63 (m, 4H), 3.93(s, 3H), 3.95 (s, 3H), 6.90 (d, 1H, J=1.8 Hz), 7.14 to 7.26 (m, 7H),7.46 (s, 1H), 7.49 (s, 1H), 7.61 (dd, 1H, J=7.9/1.8 Hz), 7.66 (d, 1H,J=8.0 Hz), 7.67 (d, 1H, J=1.3 Hz), 7.73 (d, 1H, J=7.8 Hz).

(b)2″-Methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 500 mg (1.0mmol) of the ester obtained in Example 44(a), 420 mg (86%) of20″-methoxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 272–274° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 0.91 (s, 6H), 1.26 (s, 6H), 1.55 to1.63 (m, 4H), 3.92 (s, 3H), 6.90 (d, 1H, J=1.8 Hz), 7.13 to 7.25 (m,7H), 7.45 (d, 1H, J=1.4 Hz), 7.49 (d, 1H, J=1.3 Hz), 7.62 (dd, 1H,J=7.9/1.8 Hz), 7.65 (d, 1H, J=1.6 Hz), 7.71 (s, 1H), 7.75 (d, 1H, J=8.1Hz).

Example 452″-Propyloxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetraydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Methyl2″-propyloxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 7 (a), by reaction of 500 mg (1.0mmol) of the compound obtained in Example 42(c) with 110 μl (1.1 mmol)of propyl iodide, 530 mg (98%) of the expected product are obtained inthe form of a brown-coloured oil.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.03 (t, 3H, J=7.5 Hz), 1.25 (s, 6H),1.55 to 1.63 (m, 4H), 1.86 (sext, 2H, J=6.8 Hz), 3.94 (s, 3H), 4.06 (t,2H, J=6.5 Hz), 6.90 (d, 1H, J=1.8 Hz), 7.12 (dd, 1H, J=8.0/1.8 Hz), 7.17to 7.26 (m, 6H), 7.47 (d, 1H, J=7.9 Hz), 7.50 (d, 1H, J=7.9 Hz), 7.64 to7.69 (m, 4H).

(b)2″-Propyloxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 520 mg (1.0mmol) of the ester obtained in Example 45(a), 385 mg (77%) of2″-propyloxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 216–218° C.

¹H NMR (CDCl₃) δ 0.92 (s, 6H), 1.04 (t, 3H, J=7.5 Hz), 1.26 (s, 6H),1.56 to 1.64 (m, 4H), 1.87 (sext, 2H, J=6.9 Hz), 4.08 (t, 2H, J=6.5 Hz),6.92 (d, 1H, J=1.8 Hz), 7.14 to 7.25 (m, 7H), 7.48 (d, 1H, J=7.9 Hz),7.55 (d, 1H, J=7.9 Hz), 7.66 to 7.74 (m, 3H), 7.82 (d, 1H, J=8.0 Hz).

Example 463″-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid (a) Methyl3″-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 1(d), by reaction of 700 mg (1.8mmol) of the boronic acid obtained in Example 41(g) with 420 mg (1.5mmol) of methyl 4-iodosalicylate, 550 mg (75%) of the expected productare obtained in the form of yellow crystals with a melting point of134–136° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.55 to 1.65 (m, 4H), 3.98(s, 3H), 6.88 (d, 1H, J=1.9 Hz), 7.14 to 7.31 (m, 9H), 7.51 (d, 1H,J=7.9 Hz), 7.65 (dd, 1H, J=7.9/2.0 Hz), 7.72 (d, 1H, J=1.9 Hz), 7.91 (d,1H, J=8.0 Hz), 10.82 (s, 1H).

(b)3″-Hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid

In a manner similar to that of Example 1(e), starting with 550 mg (1.1mmol) of the ester obtained in Example 46(a), 277 mg (52%) of3″-hydroxy-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 266–268° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.56 to 1.64 (m, 4H), 6.89(d, 1H, J=1.7 Hz), 7.14 to 7.25 (m, 9H), 7.28 (d, 1H, J=2.9 Hz), 7.50(d, 1H, J=8.0 Hz), 7.65 (dd, 1H, J=8.0/1.8 Hz), 7.72 (d, 1H, J=1.7 Hz),7.95 (d, 1H, J=8.2 Hz).

Example 476-[2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]nicotinicacid (a) Ethyl6-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]nicotinate

In a manner similar to that of Example 1(d), by reaction of 700 mg (1.8mmol) of the boronic acid obtained in Example 41(g) with 460 mg (1.7mmol) of ethyl 6-iodonicotinate, 650 mg (80%) of the expected productare obtained in the form of a white solid with a melting point of105–107° C.

¹H NMR (CDCl₃) δ 0.92 (s, 6H), 1.28 (s, 6H), 1.45 (t, 3H, J=7.1 Hz),1.57 to 1.65 (m, 4H), 4.44 (q, 2H, J=7.1 Hz), 6.89 (d, 1H, J=1.8 Hz),7.18 to 7.30 (m, 6H), 7.57 (d, 1H, J=7.9 Hz), 7.89 (d, 1H, J=8.3 Hz),8.10 to 8.15 (m, 2H), 8.36 (dd, 1H, J=8.3/2.2 Hz), 9.31 (d, 1H, J=2.1Hz).

(b)6-[2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]nicotinicacid

In a manner similar to that of Example 1(e), starting with 650 mg (1.3mmol) of the ester obtained in Example 47(a), 490 mg (80%) of6-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-nicotinicacid are obtained in the form of a white solid crystallized as fineneedles, with a melting point of 319–321° C.

¹H NMR (CDCl₃) δ 1.04 (s, 6H), 1.26 (s, 6H), 1.57 to 1.63 (m, 4H), 7.21to 7.41 (m, 7H), 7.58 (s, 1H), 7.65 (d, 1H, J=8.1 Hz), 8.15 (d, 1H,J=8.3 Hz), 8.41 (dd, 1H, J=8.1/1.9 Hz), 8.59 (d, 1H, J=1.8 Hz), 8.69 (d,1H, J=2.2 Hz), 9.82 (d, 1H, J=1.9 Hz).

Example 485-[2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-2-pyridinecarboxylicacid (a) Methyl5-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-2-pyridinecarboxylate

In a manner similar to that of Example 1(d), by reaction of 700 mg (1.8mmol) of the boronic acid obtained in Example 41(g) with 430 mg (1.7mmol) of methyl 5-iodo-2-pyridinecarboxylate, 600 mg (77%) of theexpected product are obtained in the form of a white solid with amelting point of 160–162° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.55 to 1.65 (m, 4H), 4.05(s, 3H), 6.90 (d, 1H, J=1.8 Hz), 7.16 to 7.30 (m, 7H), 7.57 (d, 1H,J=7.9 Hz), 7.67 (dd, 1H, J=8.0/1.9 Hz), 7.72 (d, 1H, J=1.9 Hz), 8.10(dd, 1H, J=8.2/2.2 Hz), 8.24 (d, 1H, J=8.2 Hz), 9.06 (d, 1H, J=2.1 Hz).

(b)5-[2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-2-pyridinecarboxylicacid

In a manner similar to that of Example 1(e), starting with 600 mg (1.3mmol) of the ester obtained in Example 48(a), 490 mg (84%) of5-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-2-pyridinecarboxylicacid are obtained in the form of a beige-coloured powder with a meltingpoint of 222–224° C.

¹H NMR (CDCl₃) δ 0.92 (s, 6H), 1.27 (s, 6H), 1.57 to 1.65 (m, 4H), 6.89(d, 1H, J=1.6 Hz), 7.13 to 7.30 (m, 7H), 7.58 (d, 1H, J=7.9 Hz), 7.68(dd, 1H, J=8.0/1.5 Hz), 7.73 (s, 1H).

Example 492′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-hydroxamicacid

2.00 g (4.3 mmol) of the acid obtained in Example 14, 30 ml of ethanoland 290 mg (5.2 mmol) of powdered potassium hydroxide are successivelyintroduced into a three-necked flask under a stream of nitrogen. Thereaction medium is stirred for thirty minutes at room temperature and isthen evaporated to dryness. The residue is taken up in 80 ml ofdichloromethane and 673 mg (4.8 mmol) of O-(trimethylsilyl)hydroxylamineand 645 mg (4.8 mmol) of 1-hydroxybenzotriazole (HOBT) are added. Aftercooling the reaction medium to 0° C., 915 mg (4.8 mmol) of1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) areadded and the solution obtained is stirred for one hour at 0° C. andthen for sixteen hours at room temperature. The reaction medium ispoured into a water/dichloromethane mixture and extracted withdichloromethane, and the organic phase is washed with water to neutralpH, dried over magnesium sulphate and evaporated. The residue obtainedis purified by chromatography on a column of silica eluted with amixture composed of 20% ethyl acetate and 80% heptane. After evaporationof the solvents, 530 mg (22%) of the expected product are collected inthe form of a beige-coloured solid with a melting point of 105–108° C.

¹H NMR (CDCl₃) δ 0.90 (s, 6H), 1.26 (s, 6H), 1.55 to 1.63 (m, 6H), 4.70to 5.20 (m, 2H), 6.88 (s, 1H), 7.12 to 7.27 (m, 7H), 7.49 (d, 1H, J=7.9Hz), 7.60 (d, 1H, J=8.0 Hz), 7.70 (d, 1H, J=1.3 Hz), 7.73 (d, 2H, J=8.2Hz), 7.84 (d, 2H, J=8.1 Hz).

Example 502′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-ol

In a manner similar to that of Example 1(d), by reaction of 700 mg (1.8mmol) of the boronic acid obtained in Example 41(g) with 287 mg (1.7mmol) of 4-bromophenol, 560 mg (89%) of2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-olare obtained in the form of a colourless oil.

¹H NMR (CDCl₃) δ 0.91 (S, 6H), 1.26 (s, 6H), 1.56 to 1.64 (m, 4H), 4.88(s, 1H), 6.90 to 6.94 (m, 3H), 7.14 to 7.22 (m, 7H), 7.47 (d, 1H, J=7.9Hz), 7.57 (d, 2H, J=8.0 Hz), 7.57 to 7.59 (m, 1H), 7.65 (d, 1H, J=1.9Hz).

Example 51[2′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-yl]methanol

1.80 g (3.7 mmol) of the ester obtained in Example 13(b) and 30 ml oftoluene are introduced into a two-litre three-necked flask under astream of nitrogen. The solution obtained is cooled to −78° C. and 14.7ml (14.7 mmol) of a solution (1 M in toluene) of diisobutylaluminiumhydride is added dropwise. The reaction medium is stirred for one hourat −78° C., hydrolysed with 1 N hydrochloric acid and filtered. Theorganic phase is washed with water to neutral pH, dried over magnesiumsulphate and filtered and the solvents are evaporated off. Afterevaporation of the solvents, 1.31 g (79%) of[2′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-yl]methanolare collected in the form of an orange-coloured solid with a meltingpoint of 134–136° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.57 to 1.64 (m, 4H), 1.72(br s, 1H), 4.75 (d, 2H, J=3.4 Hz), 6.90 (d, 1H, J=1.9 Hz), 7.14 to 7.28(m, 7H), 7.44 to 7.51 (m, 3H), 7.63 (dd, 1H, J=8.0/1.9 Hz), 7.67 to 7.71(m, 3H).

Example 522′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carbaldehyde

640 mg (1.4 mmol) of the alcohol obtained in Example 51, 2.50 g (28.7mmol) of manganese oxide and 50 ml of dichloromethane are mixed togetherin a 500 ml round-bottomed flask. The reaction medium is stirred fortwenty hours at room temperature, the manganese oxide is then filteredoff and the dichloromethane is evaporated off. The residue obtained ispurified by chromatography on a column of silica eluted with a mixturecomposed of 80% heptane and 20% ethyl acetate. After evaporation of thesolvents, 90 mg (14%) of the expected compound are collected in the formof a white powder with a melting point of 120–122° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.56 to 1.64 (m, 4H), 6.90(d, 1H, J=1.8 Hz), 7.14 to 7.29 (m, 7H), 7.54 (d, 1H, J=8.0 Hz), 7.66(dd, 1H, J=7.9/2.0 Hz), 7.74 (d, 1H, J=1.9 Hz), 7.84 (d, 2H, J=8.3 Hz),7.97 (d, 2H, J=8.3 Hz), 10.07 (s, 1H).

Example 534′-Methoxycarbonylmethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Benzyl4-[4-hydroxy-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenyl]benzoate

6.00 g (15.0 mmol) of the compound obtained in Example 1(e) and 140 mlof DMF are introduced into a round-bottomed flask under a stream ofnitrogen. The mixture is cooled to 0° C., 502 mg (15.7 mmol) of sodiumhydride (80% in oil) are added portionwise and this mixture is stirreduntil the evolution of gas has ceased. 1.87 ml (15.7 mmol) of benzylbromide are then added and the mixture is stirred for one hour at 0° C.and then for sixteen hours at room temperature. The reaction medium ispoured into a 2N HCl/ethyl acetate mixture and extracted with ethylacetate, and the organic phase is separated out after settling has takenplace, dried over magnesium sulphate and evaporated. The residueobtained is purified by chromatography on a column of silica eluted witha mixture composed of 20% ethyl acetate and 80% heptane. Afterevaporation of the solvents, 5.21 g (71%) of the expected product arecollected in the form of a yellow crystalline solid with a melting pointof 90–91° C.

¹H NMR (CDCl₃) δ 1.34 (s, 6H), 1.36 (s, 6H), 1.76 (s, 4H), 5.40 (s, 2H),5.47 (s, 1H), 7.11 (d, 1H, J=8.8 Hz), 7.27 to 7.30 (m, 1H), 7.38 to 7.56(m, 9H), 7.66 (d, 2H, J=8.4 Hz), 8.14 (d, 2H, J=8.4 Hz).

(b) Benzyl4′-methoxycarbonylmethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 2(a), by reaction of 1.20 g (2.44mmol) of the compound obtained in Example 53(a) with 280 μl (2.9 mmol)of methyl bromoacetate, 950 mg (70%) of the expected product areobtained in the form of a white solid with a melting point of 104–106°C.

¹H NMR (CDCl₃) δ 1.27 (s, 6H), 1.33 (s, 6H), 1.72 (s, 4H), 3.80 (s, 3H),4.67 (s, 2H), 5.38 (s, 2H), 6.95 (d, 1H, J=8.5 Hz), 7.37 to 7.54 (m,8H), 7.60 to 7.62 (m, 2H), 7.64 (d, 2H, J=8.5 Hz), 8.12 (d, 2H, J=8.5Hz).

(c)4′-Methoxycarbonylmethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

300 mg (0.53 mmol) of the compound obtained in Example 53(b), 20 ml ofmethanol and 10 ml of THF are introduced into a three-necked flask undera stream of argon. The medium is degassed with argon, 60.0 mg of 15%palladium on charcoal are introduced, the system is purged with hydrogenand the reaction medium is stirred under a hydrogen atmosphere (slightexcess pressure) for 22 hours. The catalyst is filtered off throughCelite®, the solvents are evaporated off, the product obtained iscrystallized from a mixture composed of 10% ethyl ether and 90% heptane,and 142 mg (57%) of the expected product are collected in the form of awhite crystalline solid with a melting point of 234–238° C.

¹H NMR (CDCl₃) δ 1.33 (s, 12H), 1.72 (s, 4H), 3.80 (s, 3H), 4.68 (s,2H), 6.95 (d, 1H, J=8.5 Hz), 7.33 to 7.40 (m, 2H), 7.53 (dd, 1H,J=8.5/2.3 Hz), 7.60 to 7.66 (m, 4H), 8.11 (br d, 2H, J=7.8 Hz).

Example 544′-Carboxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4′-carboxylicacid

In a manner similar to that of Example 1(e), starting with 650 mg (1.2mmol) of the diester obtained in Example 53(b), 470 mg (88%) of4′-carboxymethoxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4′-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 279–281° C.

¹H NMR (CDCl₃+2 drops of DMSO-d₆) δ 1.33 (s, 12H), 1.72 (s, 4H), 4.65(s, 2H), 6.99 (d, 1H, J=8.6 Hz), 7.38 (d, 1H, J=7.3 Hz), 7.41 (d, 1H,J=8.2 Hz), 7.53 (dd, 1H, J=8.5/2.4 Hz), 7.60 to 7.62 (m, 2H), 7.64 (d,2H, J=8.4 Hz), 8.09 (d, 2H, J=8.4 Hz)

Example 554′-(5-Ethoxycarbonylpentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid (a) Benzyl4′-(5-ethoxycarbonylpentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylate

In a manner similar to that of Example 2(a), by reaction of 1.20 g (2.4mmol) of the compound obtained in Example 53(a) with 520 μl (2.9 mmol)of ethyl 6-bromohexanoate, 1.52 g (100%) of the expected product areobtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.24 (t, 3H, J=7.1 Hz), 1.32 (s, 6H), 1.33 (s, 6H),1.42 to 1.49 (m, 2H), 1.64 (quint, 2H, J=8.0 Hz), 1.72 (s, 4H), 1.78(quint, 2H, J=7.1 Hz), 2.27 (t, 2H, J=7.6 Hz), 4.02 (t, 2H, J=6.5 Hz),4.11 (q, 2H, J=7.1 Hz), 5.38 (s, 2H), 7.03 (d, 1H, J=8.6 Hz), 7.32 to7.57 (m, 8H), 7.57 (d, 1H, J=1.5 Hz), 7.61 (d, 1H, J=2.4 Hz), 7.65 (d,2H, J=8.4 Hz), 8.12 (d, 2H, J=8.5 Hz).

(b)4′-(5-Ethoxycarbonylpentyloxy)-3″-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 53(c), starting with 620 mg (1.0mmol) of the diester obtained in Example 55(a), 420 mg (80%) of4′-(5-ethoxycarbonylpentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 177° C.

¹H NMR (CDCl₃) δ 1.25 (t, 3H, J=7.2 Hz), 1.32 (s, 6H), 1.33 (s, 6H),1.41 to 1.49 (m, 2H), 1.59 to 1.68 (m, 2H), 1.73 (s, 4H), 1.78 to 1.83(m, 2H), 2.27 (t, 2H, J=7.6 Hz), 4.03 (t, 2H, J=6.5 Hz), 4.12 (q, 2H,J=7.1 Hz), 7.04 (d, 1H, J=8.6 Hz), 7.30 to 7.38 (m, 2H), 7.53 (d, 1H,J=2.1 Hz), 7.58 (d, 1H, J=1.4 Hz), 7.63 (d, 1H, J=2.3 Hz), 7.69 (d, 2H,J=7.9 Hz), 8.16 (br d, 2H, J=6.7 Hz).

Example 564′-(5-Carboxypentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid

In a manner similar to that of Example 1(e), starting with 750 mg (1.2mmol) of the diester obtained in Example 55(a), 610 mg (100%) of4′-(5-carboxypentyloxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxylicacid are obtained in the form of a white crystalline solid with amelting point of 245° C.

¹H NMR (DMSO-d₆) δ 1.28 (s, 12H), 1.36 to 1.44 (m, 2H), 1.46 to 1.55 (m,2H), 1.68 (s, 4H), 1.69 to 1.73 (m, 2H), 2.18 (t, 2H, J=7.0 Hz), 4.04(t, 2H, J=6.0 Hz), 7.20 (d, 1H, J=8.6 Hz), 7.30 (dd, 1H, J=8.0/1.2 Hz),7.37 (d, 1H, J=8.2 Hz), 7.56 (d, 1H, J=1.1 Hz), 7.61 (d, 1H, J=2.2 Hz),7.66 (dd, 1H, J=8.6/2.1 Hz), 7.81 (d, 2H, J=8.4 Hz), 7.99 (d, 2H, J=8.3Hz).

Example 572′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide(a)2′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carbonylchloride.

6.00 g (12.9 mmol) of the acid obtained in Example 14 and 240 ml ofdichloromethane are introduced into a three-necked flask under a streamof nitrogen. 2.63 ml (13.5 mmol) of dicyclohexylamine are added dropwiseand the solution obtained is stirred for ten minutes at roomtemperature. 984 μl (13.5 mmol) of thionyl chloride are added dropwiseand the solution obtained is stirred for fifteen minutes at roomtemperature. The reaction medium is evaporated to dryness, the residueis taken up in ethyl ether and filtered and the filtrate is evaporatedto dryness. The acid chloride thus obtained is used directly in thefollowing step.

(b)2′-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide

1.03 g (2.1 mmol) of the acid chloride obtained in the above step aredissolved in 100 ml of THF. The solution thus obtained is added dropwiseto a solution composed of 2.6 ml (43.0 mmol) of aqueous 32% ammoniasolution and 20 ml of THF. The reaction medium is stirred for one hourat room temperature, poured into water and extracted with ethyl ether.The organic phase is washed with water to neutral pH, dried overmagnesium sulphate and filtered and the solvents are evaporated off. Theresidue obtained is triturated from heptane, filtered and dried. 940 mg(95%) of2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamideare collected in the form of a beige-coloured powder with a meltingpoint of 220° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.26 (s, 6H), 1.56 to 1.64 (m, 4H), 6.20(br s, 2H), 6.89 (d, 1H, J=1.3 Hz), 7.14 to 7.29 (m, 7H), 7.51 (d, 1H,J=7.9 Hz), 7.64 (dd, 1H, J=7.9/1.5 Hz), 7.72 (s, 1H), 7.74 (d, 2H, J=8.2Hz), 7.91 (d, 2H, J=8.2 Hz).

Example 58N-Ethyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide

In a manner similar to that of Example 57 (b), starting with 1.30 g (2.7mmol) of the acid chloride obtained in Example 57(a) and 4.4 ml (54.3mmol) of aqueous 70% ethylamine solution, 1.20 g (91%) ofN-ethyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamideare obtained in the form of a beige-coloured powder with a melting pointof 183° C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.28 (t, 3H, J=5.7 Hz),1.56 to 1.63 (m, 4H), 3.53 (q, 2H, J=5.3 Hz), 6.18 (br s, 1H), 6.89 (d,1H, J=1.9 Hz), 7.14 to 7.29 (m, 7H), 7.51 (d, 2H, J=7.9 Hz), 7.64 (dd,1H, J=7.9/1.9 Hz), 7.71 (s, 1H), 7.73 (d, 2H, J=8.4 Hz), 7.86 (d, 2H,J=8.4 Hz).

Example 59N,N-Diethyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide

In a manner similar to that of Example 57(b), starting with 1.30 g (2.7mmol) of the acid chloride obtained in Example 57(a) and 5.6 ml (54.0mmol) of diethylamine, 930 mg (67%) ofN,N-diethyl-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamideare obtained in the form of a beige-coloured powder with a melting pointof 113° C.

¹H NMR (CDCl₃) δ 0.85 (s, 6H), 1.25 (m, 6H), 1.27 (s, 6H), 1.56 to 1.64(m, 4H), 3.35 (br s, 2H), 3.56 (br s, 2H), 6.90 (s, 1H), 7.14 to 7.28(m, 7H), 7.47 (d, 2H, J=8.2 Hz), 7.52 (s, 1H), 7.63 (dd, 1H, J=8.0/1.4Hz), 7.68 to 7.71 (m, 3H).

Example 60Morpholin-4-yl-[2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-yl]methanone.

In a manner similar to that of Example 57 (b), starting with 1.03 g (2.1mmol) of the acid chloride obtained in Example 57(a) and 945 μl (43.0mmol) of morpholine, 900 mg (80%) ofmorpholin-4-yl-[2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-yl]methanoneare obtained in the form of a white powder with a melting point of 223°C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.27 (s, 6H), 1.56 to 1.64 (m, 4H), 3.60to 4.00 (m, 8H), 6.90 (d, 1H, J=1.7 Hz), 7.13 to 7.26 (m, 9H), 7.49 (s,1H), 7.50 (d, 2H, J=8.4 Hz), 7.63 (dd, 1H, J=7.9/1.8 Hz), 7.72 (d, 2H,J=8.4 Hz).

Example 61(4-Hydroxyphenyl)-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamide

In a manner similar to that of Example 57(b), starting with 1.04 g (2.2mmol) of the acid chloride obtained in Example 57(a), 260 mg (23.9 mmol)of 4-aminophenol and 362 μl (2.7 mmol) of triethylamine, 1.15 g (95%) of(4-hydroxyphenyl)-2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1′;4′,1″]terphenyl-4″-carboxamideare obtained in the form of a grey powder with a melting point of 231°C.

¹H NMR (CDCl₃) δ 0.91 (s, 6H), 1.26 (s, 6H), 1.56 to 1.64 (m, 4H), 6.84(d, 2H, J=8.5 Hz), 6.89 (d, 1H, J=1.2 Hz), 7.14 to 7.28 (m, 7H), 7.41 to7.44 (m, 3H), 7.51 (d, 1H, J=7.8 Hz), 7.64 (d, 1H, J=7.8 Hz), 7.72 (s,1H), 7.75 (d, 2H, J=8.0 Hz), 7.95 (d, 2H, J=8.0 Hz), 8.06 (s, 1H)

Example 62 3-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxymethyl-4′-carboxylic acid (a) Benzyl2′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-4-trifluoromethanesulphonyloxy-[1,1′;4′,1″]terphenyl-4″-carboxylate

In a manner similar to that of Example 13(a), starting with 2.00 g (4.1mmol) of the compound obtained in Example 53(a), 2.33 g (90%) of theexpected product are obtained in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.31 (s, 6H), 1.32 (s, 6H), 1.73 (s, 4H), 5.39 (s, 2H),7.24 to 7.26 (m, 2H), 7.37 to 7.48 (m, 6H), 7.60 to 7.69 (m, 2H), 7.66(d, 2H, J=8.3 Hz), 8.16 (d, 2H, J=8.3 Hz).

(b) Benzyl3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxymethyl-4′-carboxylate

1.80 g (2.9 mmol) of the triflate obtained in Example 62(a), 120 mg(0.29 mmol) of 1,3-bis(diphenylphosphino)propane (DPPP), 32 mg (0.14mmol) of palladium acetate, 50 ml of methanol, 800 μl (5.8 mmol) oftriethylamine and 5 ml of THF are successively introduced into ahydrogenation bomb. The reaction medium is confined under a pressure ofsix bar of carbon monoxide and heated with stirring at 70° C. for sevenhours. The mixture is cooled and evaporated to the maximum, the residueis taken up in saturated sodium chloride solution and extracted withethyl acetate, the extracts are washed with dilute hydrochloric acidsolution and then with water, and the organic phase is dried overmagnesium sulphate and evaporated. The residue obtained is purified bychromatography on a column of silica eluted with heptane. Afterevaporation of the solvents, 1.36 g (88%) of the expected compound arecollected in the form of a yellow oil.

¹H NMR (CDCl₃) δ 1.21 (s, 6H), 1.25 (s, 6H), 1.64 (s, 4H), 3.58 (s, 3H),5.32 (s, 2H), 7.09 (dd, 1H, J=8.1/2.0 Hz), 7.18 (d, 1H, J=2.2 Hz), 7.27to 7.38 (m, 6H), 7.53 to 7.56 (m, 2H), 7.62 (d, 2H, J=8.5 Hz), 7.79 (d,1H, J=7.6 Hz), 8.08 (d, 2H, J=8.5 Hz)

(c)3-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxymethyl-4′-carboxylicacid

In a manner similar to that of Example 53(c), starting with 450 mg (0.84mmol) of the benzyl ester obtained in Example 62(b), 330 mg (89%) of3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-carboxymethyl-4′-carboxylicacid are collected in the form of a white powder with a melting point of258–261° C.

¹H NMR (DMSO-d₆) δ 1.25 (s, 6H), 1.29 (s, 6H), 1.67 (s, 4H), 3.64 (s,3H), 7.23 (dd, 1H, J=8.0/1.8 Hz), 7.25 (s, 1H), 7.74 (s, 1H), 7.80 (s,1H), 7.92 (d, 2H, J=8.4 Hz), 8.05 (d, 2H, J=8.4 Hz).

Example 633-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4,4′-dicarboxylicacid

In a manner similar to that of Example 1(e), starting with 850 mg (1.6mmol) of the diester obtained in Example 62(b), 600 mg (88%) of3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4,4′-dicarboxylic acid areobtained in the form of a white crystalline solid with a melting pointof 343° C.

¹H NMR (DMSO-d₆) δ 1.27 (s, 6H), 1.28 (s, 6H), 1.67 (s, 4H), 7.25 (dd,1H, J=7.9/1.9 Hz), 7.31 (s, 1H), 7.69 (s, 1H), 7.78 (s, 1H), 7.91 (d,2H, J=8.4 Hz), 8.04 (d, 2H, J=8.4 Hz).

Formulation Examples

The examples which follow illustrate various pharmaceutical and cosmeticformulations based on the compounds according to the invention.

A—Oral Route

(a) 0.2 g tablet Compound prepared in Example 2 10.001 g Starch 0.114 gDicalcium phosphate 0.020 g Silica 0.020 g Lactose 0.030 g Talc 0.010 gMagnesium stearate 0.005 g

In this example, the compound according to Example 2 can be replacedwith the same amount of one of the compounds of Examples 4, 8, 14, 17,29 and 34.

(b) Drinkable suspension in 5 ml vials Compound prepared in Example 120.001 g Glycerol 0.500 g 70% sorbitol 0.500 g Sodium saccharinate 0.010g Methyl p-hydroxybenzoate 0.040 g Flavouring, qs Purified water qs 5 ml(c) 0.8 g tablet Compound of Example 4 0.500 g Pregelatinized starch0.100 g Microcrystalline cellulose 0.115 g Lactose 0.075 g Magnesiumstearate 0.010 g

In this example, the compound according to Example 4 can be replacedwith the same amount of one of the compounds of Examples 11, 18, 21, 24,39 and 48.

(d) Drinkabl suspension in 10 ml vials Compound of Example 5 0.200 gGlycerol 1.000 g 70% sorbitol 1.000 g Sodium saccharinate 0.010 g Methylp-hydroxybenzoate 0.080 g Flavouring, qs Purified water qs 10 mlB—Topical Route

(a) Ointment Compound of Example 3 20.020 g Isopropyl myristate 81.700 gFluid liquid vaseline 9.100 g Silica (“Aerosil 200” sold by 9.180 gDegussa)

In this example, the compound according to Example 3 can be replacedwith the same amount of one of the compounds of Examples 7, 14, 27, 36and 53.

(b) Ointment Compound of Example 6 0.300 g White petroleum jelly codex100 g (c) Nonionic water-in-oil cream Compound of Example 2 0.100 gMixture of emulsifying lanolin 39.900 g alcohols, waxes and oils(“anhydrous eucerin” sold by BDF) Methyl p-hydroxybenzoate 0.075 gPropyl p-hydroxybenzoate 0.075 g Sterile demineralized water qs 100 g(d) Lotion Compound of Example 3 0.100 g Polyethylene glycol (PEG-400)69.900 g 95% ethanol 30.000 g

In this example, the compound of Example 3 can be replaced with the sameamount of one of the compounds of Examples 8, 18, 24, 32, 35, 43 and 46.

(e) Hydrophobic ointment Compound of Example 1 0.300 g Isopropylmyristate 36.400 g Silicone oil (“Rhodorsil 47V300” 36.400 g sold byRhône-Poulenc) Beeswax 13.600 g Silicone oil (“Abil 300.000 cst” 100 gsold by Goldschmidt) (f) Nonionic oil-in-water cream Compound of Example5 1.000 g Cetyl alcohol 4.000 g Glyceryl monostearate 2.500 g PEG-50stearate 2.500 g Karite butter 9.200 g Propylene glycol 2.000 g Methylp-hydroxybenzoate 0.075 g Propyl p-hydroxybenzoate 0.075 g Steriledemineralized water 100 g

In this example, the compound according to Example 5 can be replacedwith the same amount of one of the compounds of Examples 29, 49, 51, 52,58 and 62.

TABLE A

Ar₁ = optionally substituted aryl or heteroaryl Hal = Br or I

TABLE B

1. A biphenyl compound substituted with an aromatic or heteroaromaticradical, characterized in that they correspond to the general formula(I) below:

in which: Ar represents an aromatic or heteroaromatic radical chosenfrom:

Z being O or S, R₁ represents —COR₉, R₂ and R₃, taken together, form a5- or 6-membered ring, optionally substituted with at least one methyl,R₄ represents H, a halogen atom, linear or branched C₁–C₂₀ alkyl, —OR₁₀,—OCOR₁₁ or a polyether radical, R₅ represents H, a halogen atom, linearor branched C₁–C₂₀ alkyl, —OCOR₁₁, —OR₁₂, mono- or polyhydroxyalkl,—NO₂,

 —(CH₂)_(n)—NHCOCH₃, —CH═CH—COR₁₃, —(CH₂)_(n)COR₁₃, n being 0 to 6,—O—(CH₂)_(m)COR₁₃, —O—(CH₂)_(m)OH, m being 1 to 12, optionallysubstituted aryl, optionally substituted aralkyl, optionally substitutedheteroaryl, a polyether radical or a —CH₂— polyether radical, R₆represents H, lower alkyl or —OR₁₀, R₉ represents —OR₁₄, H or loweralkyl, R₁₀ represents H or lower alkyl, R₁₁ represents lower alkyl, R₁₂represents H, linear or branched C₁–C₂₀ alkyl, mono- orpolyhydroxyalkyl, or optionally substituted aryl or aralkyl, R₁₃represents H, lower alkyl, —OR₁₀, aryl or

R₁₄ represents H, r′ and r″, which may be identical or different,represent H, OH, lower alkyl, mono- or polyhydroxyalkyl, optionallysubstituted aryl, an amino acid residue or a peptide residue, or r′ andr″, taken together, form a heterocycle, or a salt of the compound offormula (I), or an optical or geometrical isomer of the compound offormula (I).
 2. A compound according to claim 1, characterized in thatthey are in the form of a salt of an alkali metal or alkaline-earthmetal, or alternatively of zinc or of an organic amine.
 3. A compoundaccording to claim 1, characterized in that the lower alkyl radical ischosen from the group consisting of the methyl, ethyl, isopropyl, butyl,tert-butyl and hexyl radicals.
 4. A compound according to claim 1,characterized in that the linear or branched C₁–C₂₀ alkyl is chosen fromthe group consisting of the methyl, ethyl, propyl, 2-ethylhexyl, octyl,hexadecyl and octadecyl radicals.
 5. A compound according to claim 1,characterized in that the monohydoxyalkyl radical is chosen from thegroup consisting of the hydromethyl, 2-hydroxyethyl, 2-hydropropyl and3-hydroxypropyl radicals.
 6. A compound according to claim 1,characterized in that the polyhydroxyalkyl radical is chosen from thegroup consisting of the 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl and2,3,4,5-tetrahydroxypentyl radicals and the pentaerythritol residue. 7.A compound according to claim 1, characterized in that the polyetherradical is chosen from the group consisting of the methoxymethoxy,methoxyethoxy and methoxyethoxymethoxy radicals.
 8. A compound accordingto claim 1, characterized in that the —CH₂-polyether radical is chosenfrom the group consisting of the methoxymethoxymethyl,ethoxymethoxymethyl and methoxyethoxymethoxymethyl radicals.
 9. Acompound according to claim 1, characterized in that the aryl radical isa phenyl radical optionally substituted with at least one halogen, ahydroxyl, a nitro function, a polyether radical or an amino functionoptionally protected with an acetyl group or optionally substituted withat least one C₁–C₆ lower alkyl or alkoxy.
 10. A compound according toclaim 1, characterized in that the aralkyl radical is chosen from thegroup consisting of benzyl and phenethyl radicals optionally substitutedwith at least one halogen atom, a hydroxyl, a nitro function, apolyether radical or an amino function optionally protected with anacetyl group or optionally substituted with at least one C₁–C₆ loweralkyl or alkoxy.
 11. A compound according to claim 1, characterized inthat the heteroaryl radical is chosen from the group consisting ofpyridyl, furyl and thienyl radicals, optionally substituted with atleast one halogen, a lower alkyl, a hydroxyl, a C₁–C₃ alkoxy, a nitrofunction, a polyether radical or an amino function optionally protectedwith an acetyl group or optionally substituted with at least one C₁–C₆lower alkyl or alkoxy.
 12. A compound according to claim 1,characterized in that the amino acid residue is chosen from the groupconsisting of residues derived from lysine, from glycine and fromaspartic acid.
 13. A compound according to claim 1, characterized inthat the peptide residue is chosen from the group consisting ofdipeptide and tripeptide residues.
 14. A compound according to claim 1,characterized in that when r′ and r″ form a heterocycle, this is chosenfrom the group consisting of piperidino, morpholino, pyrrolidino andpiperazino radicals, optionally substituted in position 4 with a C₁–C₆alkyl or a mono- or polyhydroxyalkyl.
 15. A compound according to claim1, characterized in that the halogen atom is chosen from the groupconsisting of fluorine, chlorine and bromine.
 16. A compound accordingto claim 1, characterized in that they correspond to the generalformulae (II) below:

in which: Ar represents a radical of formula (b) below:

R₁, R₄, R₅, R₆, and R₇ having the same meanings as those given in claim1, R₁₅, R₁₆, R₁₇ and R₁₈, which may be identical or different, representH or —CH₃, and t is 1 or
 2. 17. A compound according to claim 1,characterized in that they are taken from the group consisting of:6-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]nicotinicacid,5-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]2-pyridinecarboxylicacid, and2-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)biphenyl-4-yl]-4-thiophenecarboxylicacid.
 18. A compound according to claim 1, for use as a medicinalproduct.
 19. A pharmaceutical composition, characterized in that itcomprises, in a pharmaceutically acceptable support, at least onecompound as defined according to claim
 1. 20. A pharmaceuticalcomposition according to claim 19, characterized in that theconcentration of said at least one compound is between 0.001% and 5% byweight relative to the total weight of the composition.
 21. A cosmeticcomposition, characterized in that it contains, in a cosmeticallyacceptable support, at least one compound as defined according toclaim
 1. 22. A cosmetic composition according to claim 21, characterizedin that the concentration of said at least one compound is between 0.001and 3% by weight relative to the total weight of the composition.
 23. Adermatological, immunoallergic, cardiovascular and/or opthalmologicaltreatment method comprising administering a composition comprising acompound according to claim 1 to a person in need of said treatment. 24.A cosmetic treatment method for repairing or combating aging of the skincomprising applying to the part of the skin to be treated a compositioncomprising a compound according to claim 1 to a person in need of saidcosmetic treatment.
 25. A dermatological, immunoallergic, cardiovascularor ophthalmological treatment method comprising administering acomposition comprising a compound according to claim 1, to a person inneed of said treatment.
 26. The method of claim 25, for treatingdermatological complaints associated with keratinization disorders. 27.The method of claim 25, for treating acne.
 28. The method of claim 25,for treating ichthyosis, Darier's diseases, palmoplantar keratoderma,leucophasia and cutaneous or mucous lichen.
 29. The method of claim 25,for treating psoriasis, cutaneous atopy, respiratory atopy or gingivalhypertrophy.
 30. The method of claim 29, for treating eczema.
 31. Themethod of claim 25, for treating dermal or epiderman proliferations. 32.The method of claim 31, for treating warts, papillomatoses anduv-induced proliferations.
 33. The method of claim 25, for treatingbullosis or collagen diseases.
 34. The method of claim 25, for treatingcorneopathies.
 35. The method of claim 25, for treating cutaneousatrophy.
 36. The method of claim 25, for combating cicatrizationdisorders or stretch marks.
 37. The method of claim 25, for combatingseborrhoea.
 38. The method of claim 25, for combating arthritis.
 39. Themethod of claim 25, for combating alopecia.
 40. The method of claim 25,for combating arteriosclerosis.